Quiz 1 Flashcards
Time elapsed since the 1st day of LMP. Precedes conception by 2 weeks.
gestational age (mentstrual age)
2 weeks from 1st day of LMP
ovulation age (post-conceptional age)
How many days/weeks is gestation?
280 days or 40 weeks from LMP (gestational age)
Naegle rule
LMP - 3 months + 1 week
What are weeks for each trimester? (gestational age)
0 - 12 // 13 - 26 // 26 - 40
If fertilization happens at day 0, what day is the morula stage? blastocyst? embryo? fetus?
In postconceptual age: Morula = 3 days Blastocyst = 4.5 (implantation) Embryo = weeks 3 - 8 Fetus > 8 weeks
_______ is the most sensitive period for teratogenicity.
3-8 weeks (post-conceptional age)
5-10 weeks (gestational age)
Developmental milestones in the fetal period: gender? fetal movement and cochlear function? viability? fat deposition? full term?
Gender = week 16 Fetal movement (felt by mother) and cochlear function = week 20 Considered viable = week 24 Fat deposits = week 32 Full term = weeks 39-40
What is the average weight of full term fetus/baby?
3400 g (7.5 lbs)
Developmental milestones in the embryonic period: partitioning of the heart? spinal cord synapses? completely formed heart?
Partitioning of the heart = middle of 4th week
Spinal cord synapses = 6-7 weeks
Completely formed heart = 7-8 weeks
Key times* in the embryonic period: neuropore closure? heart begins beating? cardiac loop?
*starred slide on ppt
Cranial/rostral neuropore = day 25 (if not anencephaly)
Caudal neuropore = day 27 (if not spina bifida)
The neural tube should be completely formed and closed by day 28.
Heart beating = day 21
Cardiac loop complete = day 28
When is the 1st prenatal visit usually?
6-8 weeks from LMP (gestational age)
Date the pregnancy
The fetal period begins when? consists mostly of what kind of development?
Fetal period
begins 8 weeks (postconceptual age) or 10 weeks (gestational age)
Primarily consists of growth and maturation
The 2nd trimester begins at week ___. Developmental milestones?
Weeks 12-13 Uterus palpable above pubic symphysis Ossification Fingers/toes Skin and nails Hair External genitalia (still ambiguous) Spontaneous movements
Crown-rump length (CRL) and gestational age
12 weeks = 6-7 cm 16 weeks = 12 cm 28 weeks = 25 cm 32 weeks = 28 cm 36 weeks = 32 cm 39/40 weeks = 36 cm
2nd trimester prenatal visit at approx _____ weeks.
15-16 weeks gestation
Offer Maternal Quad Screening (Trisomy 21 and 18)
How many weeks along is the US scheduled for? What else happens during this visit?
20 weeks GA
1 hour glu challenge test
Lung development periods and gestational age
Week 24 = canalicular period
pregnancy is now considered viable
3rd trimester prenatal visit is scheduled for ____ weeks GA.
24-28 weeks
Weeks 28 development
Vernix caseosa
Pupillary membrane disappears
A fetus born at this gestational age has ~90% change of survival.
When do you give the mother Rhogam if indicated? Who gets Rhogam?
At 28 weeks GA
Rh negative moms with a chance of having an Rh + baby
When do you obtain GBS culture?
between weeks 35-37
How often do you schedule prenatal visits after 36 weeks?
Weekly
Cervical exams, confirm presentation, signs of labor/pre-eclampsia
Low AVF is called….High AVF is called…
Low = Oligohydramnios (Olig-LOW-hydramnios) High = Polyhydramnios
Maternal physiology: Plasma volume? Red cell mass? Cardiac output? GFR?
Plasma vol = 30-50% above normal
Red cell mass = increases by 20-30% (physiological dilutional anemia)
Cardiac output = increases 30-50% (from 5 L to 7L at 32 weeks)
GFR = increases ~ 50%
Maternal CO changes (preload, SVR, HR)?
- Preload increases due to increased blood volume.
- Afterload is reduced due to reduced SVR.
- HR raises 15-20 bpm
How does SVR decrease in pregnant women?
Utero-placental circulation = High flow, low resistance system
Vasodilation
How much blood goes to uterus? What is autotransfusion?
450-750 mL (@term, 10-12% of CO)
~500 mL of blood sequestered in uteroplacental unit is “autotransfused” to maternal circ following delivery (not good for patients with heart disease).
Infant reflexes: Primitive, postural, and locomotor?
Primitive = rooting, suckling, grasping, Moro Postural = head up, parachute, maintain balance Locomotor = crawling, stepping, swimming
Discuss adaptation, assimilation, and accommodation
Adaptation = changing thinking to make sense of environment
2 components of adaptation = assimilation and accommodation
Assimilation = new info brought into existing schema
Accommodation = modifying old schema or create a new one
Example of adaptation: “Child has a pet corgi and knows it is a dog.
Thinks that all animals with fur and four legs are dogs. Child sees a cat and calls it a dog. Dad corrects her by saying ‘No, that is a cat. Cats meow and dogs bark.’ The child has new information.”
Assimilation = dogs bark (new info) and have 4 legs and fur
Accommodation = cats have 4 legs and fur, but they meow
What is temperament? What are the types?
Temperament - primary pattern of reacting to environment
Types = easy, difficult, slow-to-warm
What are the 9 dimensions of temperament?
Activity Rhythmicity Approach/withdrawal Adaptability Threshold of responsiveness Intensity of rxn Quality of mood Distractibility Attention span and persistence
Which temperament dimension?
Degree of motor activity during daily activities (bathing, eating, playing)
Activity
Which temperament dimension?
Positive or negative response to a new stimulus
Approach or withdrawal
Which temperament dimension?
How predictable or regular is the infant’s schedule?
Rhythmicity
Which temperament dimension?
Ease with which the infant modifies his/her responses when confronted with new or changing situations.
Adaptability
Which temperament dimension?
How strong does a new situation need to be to cause a change in the infant’s behavior?
Threshold of responsiveness
Which temperament dimension?
Degree to which the infant pursues and continues an activity even in the face of obstacles
attention span and persistence
Preterm births are ____ overall.
decreasing
Low birth weight (LBW) births are ____, particularly the ELBW (extremely low birth weight) infants.
increasing
This prevents a decrease in infant/neonatal mortality rate.
What are 3 factors that have decreases infant mortality in the past?
ventilators
surfactant
antenatal steroids
When is the perinatal? neonatal period?
Perinatal = 28 weeks gestation - 28 days Neonatal = Birth - 28 days
What gestation age is considered preterm?
What are the weights in grams and death risks associated with LBW, VLBW, ELBW?
LBW =
Anemia of prematurity is due to ….
frequent blood draws
Tx for patent ductus arteriosus
indomethacin
Macrosomia
> 4000 g
Commonly seen in infants of diabetic mothers.
Increased risk of brachial plexus injuries during vaginal delivery.
Describe how infant of diabetic mothers (IDM) develop RDS…
Hyperinsulinemia –> inhibits cortisol –> decreased surfactant production
How do IDM develop kidney problems?
Renal vein thrombosis and hematuria due to…
- Polycythemia
- Decreased CO 2ndary to hypertrophic cardiomypathy
Multiple genes with additive effect (explains quantitative effects).
Human examples?
Polygenic genes
Height, weight, IQ, BP
Small quantitative effect on the level of expression of another gene.
“Modifier” genes
Transmission of info from cell to daughter cells w/o info encoded in nucleotide sequence
Epigenetics
- Does NOT follow Mendelian inheritance
- Somatically inherite* (not transmitted through meiosis)
*Somatic mutation, genetic alteration acquired by a cell that can be passed to the progeny of the mutated cell in the course of cell division.
Examples of epigenetics
X-inactivation Imprinting DNA methylation histone/chromatin modification RNA modifiers (non-coding DNA)
Examples of genetic susceptibility to environmental factors
Fetal hydantoin syndrome (epoxide hydrolase)
Outcomes in head trauma
ApoE polymorphisms
Genetic deficiencies in ____ activity have been linked w/ aggression.
Monoamine oxidase A (MAOA)
- x-linked gene
- decreased levels associated with development of antisocial behavior with maltreatment
Gene expression linked with child abuse and suicide
Hipocampal NR3C1 (neuron specific glucocorticoid receptor) - decreased in victims with a history of child abuse
Mechanism of maternal obesity induced programming in offspring
147 genes altered (most involved in lipid/carb metabolism)
SREB1 - master lipogenic factor (insulin-induced transcription factor, UP-regulated)
AMPK/PPAR-alpha - FA oxidation, down-regulated
The expression of a train in ONLY one of the sexes due to anatomical differences
sex-limited phenotype
A phenotype which occurs in both males and females but with different frequencies
Sex-influenced phenotypes
Huntington’s disease = atrophy of the _____ nucleus.
Caudate
CAG tri-nucleotide repeat
In Huntington’s disease, age of onset correlated with size of CAG repeat – but this only accts for 50% of variability in onset. What other gene variations are responsible?
TP53
Human Caspase Activated DNase (hCAD) genes
Bilateral lip pits
Van derWoude syndrome - a gene at chromosome 17 w/ the VWS gene at chromosome 1
Epigenetic gene regulators can be found in _____…
Non-coding region of DNA/RNA (ncDNA)
different genes at different loci produce the same phenotype
Genetic (locus) heterogeneity
Virchow’s triad
Vessel wall abnormalities - atherosclerosis Changes in blood composition - thrombosis Venous stasis (e.g. long-distance air travel, environmental)
Genes associated with atherosclerosis (lipid metabolism)
Lipoprotein A Apolipoproteins Cholesterol ester transfer protein Lipoprotein lipase Paraoxynase
Genes associated with atherosclerosis (Blood pressure)
ACE
Angiotensin receptor, type 1
Angiotensinogen (AGT)
Processes involved in atherosclerosis
Lipid met BP Inflammation/Leukocyte adhesion - VCAM, CRP, MCP-1 Insulin resistance - pear-shaped body type Endothelial properties - connexin, collagen I + III, laminins
Rare genetic disorder characterized by…
MR, marfanoid habitus, lens dislocations, thrombosis
Homocystinuria - elevated levels of homocysteine.
- Cystathione beta-synthase (CBS)
- Methylene Tetrahydrofolate reductase (MTHFR)
- methionine synthase (MS)
Protein ____ deficiency can lead to a state of hypercoagulability. This disease has a severe form of thrombosis called _____.
Protein S
Purpura fulminans - severe clotting throughout the body
Whats the difference between types 1 and 2 anti-thrombin III deficiencies?
Type 1 = not enough ATIII
Type 2 = adequate ATIII levels, but does NOT function properly
Hereditary causes of VTE
Dysfibrinogenemia Homocystinuria Protein C def Protein S def ATIII def (I and II) Prothrombin (factor 2) mutation Activated Protein C resistance - Factor V Leiden Mutation Hyper-homocysteinemia - MTHFR, CBS mutations
What is Protein C’s normal activity in the coag cascade?
Protein C degrades Factors V and VIII
MTHFR C667T mutation is assoc with increased risk of…
Arterial + Venous thrombi NTD's Pregnancy loss Placental abruption Hypoxic-ischemic encephalopathy (HIE)
Modes of transmission for infections - Congenital, perinatal, and neonatal?
Congenital = hematogenous spread Perinatal = vertical transmission Neonatal = environmental
Which bugs are in the infection prenatal screen?
Rubella Syphilis HIV GBS Chlamydia Gonorrhea Hep B + C
What does TORCH stand for?
Toxoplasma Other (HIV, Syphilis) Rubella CMV Herpes
CMV
Most common utero viral infection
- 90% asymptomatic at birth, develops hearing loss later
- Thrombocytopenia
- Tx: Gancyclovir (improves hearing outcome), can lead to pancytopenia
Syphilis
Treponema pallidum Screen = RPR, VRDL Dx = FTA-Abs (+ for life) Presentation: - Maculopapular rash on palms/soles - Hutchinson teeth Tx = penicillin
HIV
Dx at birth = HIV DNA PCR
- 14 -21 days, 1-2 mo, 4-6 mos
Tx within 6 hrs = AZT
Avoid breast feeding
Neonatal sepsis defined as…
Clinical syndrome in an infant
Early onset vs late onset neonatal sepsis
Early = perinatal, within 48-72 hours of birth
- vertical transmission only
(Exception GBS sepsis can present as early or late)
Late = after 3 days of life (up to 7 days for GBS)
- vertical OR horizontal transmission
What is horizontal transmission?
Environment or care-providers infect neonate
What are the major bugs of early onset neonatal sepsis? late onset?
Early = GBS, E. coli
Late = GBS, E. coli + Staph aureus
GBS infection in pregnant women can lead to…
premature rupture of membranes and preterm delivery
What is the most important test for definitive dx of neonatal sepsis?
Blood culture!
What is the treatment for early onset neonatal sepsis? late onset?
Early = Ampicillin + gentamicin
Late = Amp + Gent + Staph coverage (vanc or naf)
Chlamydia
- causes fever, cough, conjunctivitis within 6 weeks of life
- Tx for mom = Azithromycin
- Tx for baby = Erythromycin
Intacytoplasmic inclusion bodies
Neonatal herpes simplex
85% perinatal infection - suspect up to 6 weeks of age - tx acyclovir Labs: - thrombocytopenia - acute liver failure - CSF pleocytosis Presentation - mucocutaneous vesicles - seizures - neural deficits
Disseminated candida
thrombocytopenia
hyperglycemia
high mortality
associated with w/d of long-term abx tx
Common causes of Respiratory distress (5)
- respiratory distress syndrome
- meconium aspiration syndrome
- pneumonia
- transient tachypnea of the newborn
- bronchopulmonary dysplasia
Signs/symptoms of respiratory distress
nasal flaring grunting retractions tachypnea (> 60) decreased air entry cyanosis
Stages of lung development + gestational age
Embryonic = 0-5 wks - trachea + bronchi Psuedoglandular = 5-16 wks - non-respiratory bronchioles Canalicular = 16 - 25 wks Terminal Sac = 25-36 wks - Alveolar ducts Alveolar > 36 weeks
RDS features
Radiographic: - Ground-glass appearance - homogenous, symmetrical - Air bronchograms Histologic = hyaline membranes + collapsed alveoli
Which lung cells produce surfactant?
Type 2 pneumocytes
How does surfactant work?
decreases surface tension and maintains alveolar distention
LaPlace’s Law = smaller radius, higher P
Meconium Aspiration syndrome
Term baby
Fluid stained with meconium
Radiologic features: -Coarse markings - asymmetrical - hyperinflation/consolidation - air leaks (pneumothorax) MoA: - mechanical and chemical obstruction - surfactant inactivation - increased pulmonary resistance
Persistent pulmonary HTN of the newborn (maladaptation vs maldevelopment)
Maladaptation = increased PVR due to hypoxia, asphyxia, sepsis or aspiration
Maldevelopment = PVR due to abnormal pulmonary vascular bed.. pulmonary hypoplasia or diaphragmatic hernia
Increased PVR leads to ____ pulmonary blood flow and _____ to ____ shunt.
Decreased
R –> L shunt
Transient tachypnea of the newborn is associated with what kind of delivery? explain.
Full term baby delivered by C-section
Vaginal delivery usually helps squeeze out amniotic fluid in lungs.
What are indications that respiratory distress is due to cardiac cause (not pulmonary)?
Cyanosis unrelieved by 100% O2
What are the 5 T’s of cyanotic heart disease?
Transposition of the great vessels Truncus arteriosus Tricuspid atresia Tetralogy of Fallot Total anomalous pulmonary venous return
Define pneumothorax
air between the parietal and visceral pleura
Decreased breath sounds and increasing chest diameter on affected side
Deviation of trachea
What do you do for diaphragmatic hernia?
Immediate intubation
Bronchopulmonary dysplasia
cystic areas interstitial fibrosis atelectasis hyperinflation caused by prolonged O2 use
Where is the mtDNA content highest?
brain > muscle > heart > kidneys > liver
high ATP demand
What is replicative segregation/drift?
Homosplasmic vs heteroplasmic
Cytokinesis with partitioning of different mitochondria into different daughter cells
Homoplasmic = single mtDNA sequence in given cell (each daughter cell with have same mtDNA)
Heteroplasmic = more than 1 mtDNA sequence in other cell (each daughter cell will have different mtDNA)
Mitchondrial DNA pattern of inheritance
Maternal inheritance =
Only females pass it on, and ALL offspring are affected
Bottleneck phenomenon
Restriction and subsequent amplification of mitochondrial DNA in oogenesis
Reduces diversity!!
Example of threshold expression of phenotype
Aminoglycoside toxicity (oto-) - A1555G confers sensitivity to aminoglycosides
What are some general features of mitochondrial DNA?
circular double stranded no introns different DNA code than nuclear DNA higher mutation rate
When does OXPHOS activity (# of mitochondria) rise then decline?
Rises in last half of gestation and first 10 years of life
Gradual decrease to adult levels by about 20 years old
Semiautonomous inheritance
Mitochondrial DNA replicates and segregates in daughter cells INDEPENDENT of nuclear chromosomes
What is DIDMOAD?
Diabetes insipidus
Diabetes mellitus
optic atrophy
and deafness
due to mitochondrial mutations and/or autosomal gene on 4p16
Is there a correlation between genotype and phenotype when it comes to mtDNA mutations?
NO!
dissociation of genotype and phenotype –> wide-range of intrafamilial variability
Discuss how mitochondria are associated with the aging process.
Somatic mutations accumulate in post-mitotic tissues with age
What does the clinical phenotype of mitochondrial dysfunction depend on?
- Level of heteroplasmy
- Distribution of heteroplamsy (which cells affected?)
- modifier genes (nuclear genome)
- Time (allows for more mutations)
- Threshold effect
44% of the mitochondrial disorders present in childhood as ______ problems.
Neuromuscular
- weakness and elevated CPK levels
Remaining 56% are non-neuromuscular (liver, heart, kidney, GI, endocrine, hematologic, dermatologic)
List some of the adult presentations of mitochondrial disorders
vision loss myopathies ataxia neuropathy diabetes deafness
What are ragged red muscle fibers? ** (IMPORTANT)
- Pathognomonic for mitochondrial disorder!!
- Abnormally shaped cristae, paracrystalline inclusions, clumped oxidative enzymes, increased neutral lipids in muscles
With mitochondrial syndromes, multiple phenotypes are associated with the same mutation. True or False?
True!
What are lamins?
Multifunctional filamentous proteins of the nuclear lamina, just under the inner nuclear membrane
Hutchinson-Gilford Progeria is caused by…
mutation in nuclear lamins
progeria = premature aging
Glycosylation occurs in which subcellular organelle?
Rough endoplasmic reticulum
What test do you run for congenital disorders of glycosylation?
Transferrin isoelectric focusing
- proteins will have different migratory patterns
CDG Type 1 - interesting clinical feature according to Schaeffer?
Inverted nipples
Hunter syndrome is an example of ___________ disease.
Lysosomal storage disease
Hunter syndrome =
x-linked (only boys affected), mucopolysaccharidosis,
hydrolase deficiency
Zellweger syndrome is a type of ______ dysfunction.
Peroxisome
Epidermolysis bullosa is associated with which subcellular organelle?
cytoskeleton
Epidermolysis bullosa - blistering of skin, caused by mutation in cytoskeletal keratins, keratin-5, or keratin-14 genes
Cilia and flagella have a _____ structure.
9-2 dynein
______ syndrome is an example of disorder of motile cilia.
Kartagener syndrome (also called primary ciliary dyskinesia)
- situs inversus
- infertility
- chronic respiratory abnormalities
Germinal matrix (GM) hemorrhage and grading
Grade:
1 = caudo-thalamic groove
2 = intraventricular hemorrhage w/ normal sized ventricles
3 = intraventricular hemorrhage w/ dilation
4 = parenchymal hemorrhage
Does GM hemorrhage occur in full-term babies?
NO!
Only occurs in pre-term babies because the GM is gone by 35 weeks gestation.
By 32 weeks, GM is only at the caudothalamic groove (grade 1)
GM hemorrhage associated with…
LBW and cyanotic congenitla heart disease
Premature infant or full term infant with CHD
abdominal distention, increased residuals, blood in stool
apnea and bradycardia
acidosis
… What is this clinical picture describing?
Necrotizing Enterocolitis
Buzz words (3 P’s) for NEC
Pneumatosis intestinalis
Pneumoperitoneum
Portal venous gas
What are the upper GI findings of mid-gut volvulus?
duodenum not retroperitoneal
duodenal obstruction
corkscrew duodenum
Contrast will very slowly leak past the volvulus
double bubble sign
duodenal atresia (could also be annular pancreas)
No contrast leaks past the atresia!
What condition is duodenal atresia associated with?
Down syndrome
30% have trisomy 21
Hirschsprung’s
Absent ganglion cells in a portion of the colon
Rectosigmoid ration
Small left colon syndrome
AKA meconium plug syndrome or immature colon
infants of diabetics
splenic flexure transition
self-limiting
Ileal atresia
Micro-colon - these babies never get meconium in their colon to cause it to dilate
Due to an ischemic event in utero
significant narrowing or complete absence of portion of small bowel
Which brain imaging do you do first in neonates?
Ultrasound
Windows for imaging =
anterior and posterior fontanelles
mastoid
Cavum septum pellucidum
is a persistence of the embryological fluid-filled space between the leaflets of theseptum pellucidumand is a common anatomical variant. The CV is sometimes referred to as the 6th ventricle.
What is the most common ischemic brain injury in premature infants?
Periventricular leukomalacia - white matter adjacent to the ventricles. Results from hypotension, ischemia, and coag necrosis at the border or watershed zones of deep penetrating arteries of the middle cerebral artery (MCA)
(also a complication of GM hemorrhage)
Neonatal hypoxic ischemic injury
compromised gas exchange
marked redistribution of blood flow
- increase in flow to brain, heart, and adrenals
- decrease in flow to kidneys, bowel, and skin
