Week 6 Flashcards
Pregnant woman with aortic stenosis
Mother with aortic stenosis can cause issues in pregnancy (regurgitant lesions are better tolerated during pregnancy)
Plasma volume and RBC mass during pregnancy
Both increased
Plasma volume increased to greater extent though, leading to dilutional anemiai
CO in pregnancy
Increased CO by 40% (increase in HR and SV)
- Mostly distributed to Breasts, skin, uterus, and kidneys
- NO change in brain or liver
- Physiologic sinus tachycardia can occur
- Systolic murmurs can be physiologic, and S3 is common
- Can get more frequent arrhythmias
Vascular resistance in pregnancy
Decreased vascular resistance (via progesterone)→ decreased BP, decrease in afterload
Preload and pregnancy
Increased preload (increased venous return) = increased EDV
Cardiac compliance and myocardial contractility in pregnancy
Increased cardiac compliance and myocardial contractility
Specific cardiac physiologic responses that happen during labor
Further increase in CO during contraction via sympathetic stimulation and pushing of blood from placenta to systemic circulation (during contraction)
Specific cardiac physiologic responses that occur postpartum
Acute increase in CO in first hour
Return to prepregnant baseline over weeks to months
Pathology of cardiovascular adaptations in pregnancy
1) Pre-eclampsia = new HTN, proteinuria, edema
2) Preexisting HTN:
- Intrauterine growth retardation
- Pre-eclampsia superimposed on chronic HTN
Respiratory rate in pregnancy
unchanged
PaCO2 and PaO2 in pregnancy
PaCO2 DECREASES, oxygen consumption and PaO2 INCREASES
pH increases, serum HCO3- decreases - *Pregnancy is a state of primary respiratory alkalosis with a compensatory metabolic acidosis
FEV1 and FEV1/FVC in pregnancy
unchanged
Vital capacity in pregnancy
unchanged
Tidal volume in pregnancy
INCREASES - due to increased chest AP diameter and chest circumference
Inspiratory capacity in pregnancy
increased
Inspiratory reserve volume in pregnancy
Unchanged
FRC, ERV, RV, and TLC in pregnancy
all decreased
GI Tract Physiology in pregnancy:
- Calori intake
- saliva production
- gastric emptying, motility
- risk of peptic ulcer disease
- risk of GERD
- frequency of constipation
- cholestasis and cholesterol
- Increased caloric intake required (around 200 kcal/day)
- Increased saliva production (Ptyalism)
- Decreased gastric emptying, reduced intestinal motility
- Decreased risk of peptic ulcer disease
- Increased risk of GERD (decreased LES tone due to progesterone)
- Increased frequency of constipation
- Increased cholestasis and cholesterol hypersecretion
Liver and pregnancy
- Increased alkaline phosphatase
- Decreased serum albumin and total protein (hemodilution)
- Spider angioma, palmar erythema
Total body water in pregnancy
Increase in TBQ from 6.5 → 8.5 L
Chronic volume overload with active sodium and water retention → hemodilution, weight gain, anemia, elevated CO
Impaired volume expansion →
Increased risk for preeclampsia
Impaired fetal growth / fetal growth restriction
Osmoregulation in pregnancy
Increased water retention > sodium retention
Increase in all components of RAAS
ANP and BNP in pregnancy
increase
Kidneys in preg
enlarge
Bladder in pregnancy
Bladder capacity decreases (due to enlarging uterus) but increased urine volume
GFR and RPF in pregnancy
Increased GFR, increased RPF even more → filtration fraction (GFR/RPF) decreased
2 pathological changes to kidney in pregnancy
Relative hydronephrosis of pregnancy
Increased risk of pyelonephritis due to urinary stasis and asymptomatic bacteriuria
Pregnant patients with chronic renal insufficiency
can have increased risk of complications and worsen their renal diseas
Hematocrit and platelets in pregnancy
Hematocrit: Blood volume increases, RBC mass only increases slightly → Hemodilution and physiologic anemia
Platelets: hemodilution, thrombocytopenia
Immune system in pregnancy
Increased peripheral WBCs - upper limit of normal is 12,000
During labor can get WBC count up to 20,000-30,000
Want to develop immune tolerance to developing fetus
Successful pregnancy dependent on evasion of immune surveillance or suppression of maternal adaptive response
Coagulation factors in pregnancy
Want to decrease risk of hemorrhage → increase total clotting factors, decrease in fibrinolytic system
Factor 11 and 13 are the only clotting factors that decrease
Protein C = Constant
Protein S = Sinks (goes down)
No evidence of increased coagulability
Increased risk for DVT/PE (treat with unfractionated or LMW heparin)
Dermatologic changes in pregnancy
Hyperpigmentation - melasma, darkening of linea nigra, areolae, nipples, genital skin, axillae
hCG stimulates MSH
Increased blood flow to skin
Hyperemesis gravidarum:
refractory vomiting/nausea + weight loss, dehydration, electrolyte imbalance, ketonemia
Associated with increased levels of hCG (multiple gestion)
Treatment: B6 + doxylamine, diet changes
Cholestasis of pregnancy
Most common liver disorder in pregnancy
Progesterone → decreased tone and motility, gallbladder hypomotility
Increased frequency of gallstones
Presentation of cholestasis of pregnancy
itching on palms and soles + generalized itching WITHOUT rash
Mild jaundice, mild elevations in AST, ALT
Can be associated with still birth
Tx of cholestasis of pregnancy
low fat diet and possibly elective cholecystectomy
Surgery considered after 1st trimester
Placenta polypeptide hormone production
CRH, GnRH, GHRH, TRH
hCG, hPL, hPGH
Leptin, neuropeptide Y, inhibin, activin, chorionic ACTH, relaxin, PTH-rp
Placenta steroid hormone production:
Estrogen
Progesterone
1,25-OH Vit D
Human chorionic gonadotropin (hCG):
Glycoprotein
Produced 8 days after ovulation → doubles every 48 hrs for 1st 5-6 weeks
Peaks at 10-12 weeks
Activity of hCG (8)
- *Maintains corpus luteum in early pregnancy (until 8-10 wks)
- Regulate differentiation of cytotrophoblasts → syncytiotrophoblasts
- Controls trophoblastic invasion
- Induces apoptosis of endometrial T cells → promote immune survival
- Stimulate fetal Leydig cells to produce testosterone
- Can cause hyperemesis
- Stimulates RELAXIN → increases GFR and RBF, and decreases SVR
- Has TSH activity → lower TSH levels early on
hCG clinical correlates (5)
- hCG induced hyperthyroidism
- hCG > 1500 → no gestational sac, ectopic
- hCG > 9000 → no cardiac activity
- Increased hCG → Down’s
- Decreased hCG → trisomy 18
Human placental lactogen (hPL):
participates in metabolic adjustments that deliver nutrients to developing fetus
- Similar to GH and PRL
- Secreted by syncytiotrophoblasts
- Secretion rate parallels placental weight
- Detected 5-10 days → peaks at 32 weeks
- Made in massive quantities (1-2 g/day)
Activity of hPL
Stimulates insulin secretion (also has some anti-insulin effects)
Mobilization and utilization of FFAs for energy by increasing lipolysis
Weak GH activity → promotes growth of mammary tissue
Human placental growth hormone (hPGH):
contributes to insulin resistance of pregnancy
Secreted by syncytiotrophoblasts
Differs from GH only by 13 aa - NOT regulated by
GHRH, but binds same receptor
Secreted tonically, REPLACES pituitary GH later in pregnancy
Activity of hPGh
Anti-insulin effects → maternal insulin resistance necessary to shunt glucose and aa to fetus to ensure adequate growth
Pre-existing insulin resistance → gestational diabetes
Growth hormone effects
Progesterone in pregnancy
Critical to maintain pregnancy
Corpus luteum produces it prior to 8-11 weeks → then made by placenta
Biosynthesis of progesterone in pregnancy
dependent on LDL receptors on trophoblast plasma membrane
Maternal cholesterol → pregnenolone (placental) → progesterone
Progesterone → fetal adrenal gland → DHEAS
DHEAS → placenta for conversion to estriol and estrone
DHEAS → fetal liver → 16-OH DHEAS → estriol (in placenta)
Activity of progesterone (8)
- Promotes decidua formation
- Substrate for synthesis of cortisol and aldosterone in fetal adrenal cortex
- Inhibits uterine contractions
- Modulates immune system (promotes Th2 and suppress Th1)
* *Can improve Grave’s in third trimester - Stimulates minute ventilation
- Smooth muscle relaxant (GI, uterus, GU)
- Promotes lobular development in breast → inhibit milk secretion
- Contributes to decreased SVR
Estrogen in pregnancy
Levels may increase 100x
High levels of placental aromatase
DHEAS → estrogens by placenta
90% of estradiol secreted into maternal circulation
10 activities of estrogen
- Stimulates growth of myometrium
- Induces hypercoagulable state → thrombosis
Leading cause of maternal mortality
**Causes proliferative retinopathy to worsen - **Increases Thyroid Binding Globulin
- Induces lactotrophs (increases PRL)
- Peripheral vasodilation
- Increases CO, increases HR
- Increases uterine blood flow and decreases resistance
- Increases blood volume, renal perfusion and GFR
- Increases TG synthesis → Pancreatitis
- Increases pituitary size and vasculature → Sheehan’s syndrome
Trophoblastic cell type responsible for hormone production
Syncytiotrophoblasts
Hemochorial endothelial placentation
MOST placental hormones secreted exclusively into maternal circulation
Bathed directly by maternal blood within intervillous space, separated from fetal blood by several layers of tissue
Net transfer of steroids and polypeptide hormones to maternal blood is»_space; fetus
Cytotrophoblasts and hormone production
can synthesize some peptide hormones, but no steroid hormones
Placental transfer of hormones
More permeable to lipid soluble molecules
Hormones actively metabolized by placenta (T4 → T3, and cortisol → cortisone
Changes in carbohydrate and fat metabolism in pregnancy:
LATER ON:
CATABOLIC
Insulin resistance: NORMAL in pregnancy (later on)
- Physiologic adaptation to ensure adequate nutrients to fetus
- Human placental growth hormone is main anti-insulin hormone
- Must increase insulin secretion by 2-3x in pregnancy to maintain euglycemia
Catabolic state with increased lipolysis, glycogen store depletion
→ shift from carb to fat metabolism and conserve glucose for fetal-placental unit resulting in increased ketones
Prolonged fasting → starvation ketosis → high risk of DKA in pregnancy
Changes in carbohydrate and fat metabolism in pregnancy:
Early ON:
ANABOLIC → storage of fat
Insulin sensitive 1st trimester: can get INCREASED sensitivity to insulin → severe nocturnal hypoglycemia in 1st trimester
Gestational diabetes
glucose intolerance recognized for the first time during pregnancy
Prevalence has doubled in 10 years due to obesity epidemic
Risk factors gestational diabetes
- Obesity/Overweight
- Insulin resistant
- Thin GDM women often GAD ab positive → risk for autoimmune DM (type 1)
Pathogenesis of gestational diabetes
- Marked decrease in insulin mediated glucose disposal
- Impaired glucose transport into skeletal muscle and adipose tissue
- B-cell cannot compensate for insulin resistance despite hyperinsulinemia → hyperglycemia
- BOTH first and second phase insulin secretion impaired
- Hepatic overproduction of glucose
Fetal response to gestational diabetes (6)
- Macrosomia (LGA = large for gestational age) - Fetal overgrowth
- Pancreatic hyperplasia, cardiac hypertrophy - Shoulder dystocia
- Increased mortality because they overgrow their blood supply
- Infant respiratory distress syndrome
- Neonatal hypoglycemia, from hyperinsulinemia
- Hyperbilirubinemia and polycythemia
Complications with gestational diabetes
Most never return to normal insulin sensitivity → HIGHER risk of T2DM later on
Higher risk of infection, C-section, Preeclampsia
Thyroid function and pregnancy:
Increase in TBG → increased TOTAL T4
Free T4 and T3 normal
TSH normal or slightly low in 1st and 2nd trimester (due to hCG)
Fetal thyroid function:
Fetal brain dependent on mom’s T4
T4 transporters in fetal brain, no T3 → do NOT use T3 in pregnancy
B-hCG and TSH:
hCG has same a-subunit as LH, FSH, and TSH
Iodine deficiency
Leading preventable cause of mental retardation
Cretinism: due to both maternal and fetal iodine deficiency
Baby needs iodine to make thyroid hormone
Maternal Hypothyroidism:
Typically due to Hashimoto’s
Must increase thyroid hormone dosage because of increased TBG and T4 crossing placenta
Maternal Hyperthyroidism:
**hCG can induce hyperthyroidism
Grave’s Disease → can cause fetal problems because thyroid hormone AND antibodies cross placenta to stimulate fetal thyroid hormone production → fetal tachycardia, IUGR, premature
When hCG levels are… what stage is the pregnancy in?
1,500 IU/mL hCG→
4,000 IU/mL hCG→
1,500 IU/mL hCG→ + Intrauterine pregnancy seen by transvaginal US (around 5-6 weeks gestational age)
4,000 IU/mL hCG→ + IUP by transabdominal US (around 7 weeks gestational age)
Ectopic pregnancy
hCG LOWER than expected
1/150 pregnancies
Typically implantation in fallopian tube
Can cause hematosalpinx
35% with prior PID
Diagnosis: clinical symptoms, B-hCG, ultrasound
Gestational trophoblastic disease
abnormal growth of cells that would normally develop into the placenta
Can be benign or malignant
Some due to abnormal conception/pregnancy
Some true neoplasms → uncontrolled tumor-forming proliferation of malignant trophoblast
**Massively elevated hCG around 5-6 weeks
Complete or partial mole
Need both maternal and paternal DNA for normal development
what does mom’s DNA develop? what about dad’s?
what happens when you have too much paternal DNA?
Mom → embryonic tissue
Dad → Placental tissue
Too much of Dad’s DNA → overgrowth of placental type cells
Complete Mole
chromosome number?
mechanism?
diandric DIPLOID (46, XX or XY)
One sperm fertilizes anucleate egg and divides (85%) OR two sperm fertilize anucleate egg (15%)
ALL genetic material is paternally derived
Complete Mole
Classic appearance on US (4)
1) “cluster of grapes”
2) “snowstorm” appearance
3) cystically dilated spaces WITHOUT fetal parts (NO mom DNA)
4) placental overgrowth
Complete Mole
Appearance (5)
1) “Grape-like vesicles”
2) Abnormal placental tissue with NO fetal development
3) Circumferential trophoblastic hyperplasia **
4) ABSENT staining of villous stromal cells
5) **HYDROPIC Vili (edemetous, watery)
Complete Mole
Presentation (5)
1) Typically present in second trimester
2) Vaginal bleeding, anemia
3) Vaginal passage of “grape-cluster” hydropic molar vesicles
4) Uterine size larger than would be expected
5) EXTREMELY elevated B-hCG (>100,000)→ hyperemesis gravidarum, early pre-eclampsia, hyperthyroidism, theca-lutein ovarian cysts
Complete Mole - what are the risks? (2)
1) 20% of complete moles develop persistent GTD (PREMALIGNANT CONDITION)
2) Most common precursor of CHORIOCARCINOMA (1-2% progress)
Choriocarcinoma
Presentation
-most common precursor is hydatidiform mole
Can be widely metastatic at discovery, but highly chemosensitive
Frequently metastasizes hematogenously (rather than lymphatically) –> Lung > vagina»_space;> brain, liver, kidney
Choriocarcinoma
Appearance (5)
1) single/multiple hemorrhagic, well-circumscribed nodules in uterus
2) soft yellow-white tumor with large areas of ischemic NECROSIS and HEMORRHAGE
3) **Biphasic pattern (cytotrophoblasts = MONOnuclear, syncytiotrophoblasts = MULTInuclear)
4) Marked nuclear atypia and mitoses
5) No chorionic villi*
Treatment for complete mole (3)
1) D&C (dilation and suction Curettage)
2) MUST administer Rh Ig (Rhogam) at time of D&C because Rh(D) expressed on trophoblastic cells
3) Monitor hCG levels for signs of invasive mole/choriocarcinoma –> MTX if present
Partial Mole
chromosomes?
mechanism?
diandric TRIPLOID (69, XXY)
Two sperms fertilize one egg
Partial Mole
US appearance (2)
large cystic spaces +/- fetal tissue - subtle
Partial Mole
Histology (4)
1) admixture of hydropic and fibrotic villi
2) “Lacy” trophoblast hyperplasia
3) Villous inclusions
4) Association with fetal syndactyly (fusion of digits)
Partial Mole
Complications?
Virtually no partial moles recur/progress (unlike complete hydatidiform mole)
Placental Site Trophoblastic Tumor (PSTT)
neoplastic proliferation of EXTRAvillous trophoblast (VERY rare)
5-8% develop after molar pregnancy
Hysterectomy usually curative
Placental Site Trophoblastic Tumor (PSTT)
Appearance
Infiltrative mass + sheets and cords or trophoblasts growing between muscle fibers
Invasion into myometrium NOT in presence of pregnancy
Maternal surface of placenta
maternal surface of the placenta appears bumpy due to cotyledons (separations of the decidua basalis composing an individual chorionic villus).
Fetal surface of placenta
fetal surface of the placenta appears smooth and pink or blue, with visible chorionic blood vessels that join to form the umbilical cord.
Fetal:Placental Weight Ratio
reflects balance between fetal and placental growth → Increases with gestational age
What structures are in the umbilical cord? (4)
R and L umbilical umbilical arteries
Left umbilical vein
Wharton’s Jelly (mucous connective tissue)
Allantoic duct
What conditions are associated with single umbilical artery? (5)
Congenital cardiovascular abnormalities
Restricted intrauterine growth
Prematurity
Genitourinary malformations
Chromosomal anomalies
Function of umbilical arteries and vein?
TWO umbilical arteries carry DEOXYGENATED blood from the fetus to the placenta
SINGLE left umbilical vein carries OXYGENATED blood from the placenta to the fetus.
What happens if the umbilical cord is too long or too short?
Longer cord (> 75 cm)→ fetal entanglement (possible hyperactivity later in life)
Shorter cord (< 30 cm) → decreased fetal movement and neurodevelopmental problems
Chorionic plate vs. decidua basalis - what is the space in between called?
Maternal space (INTERvillous) -between chorionic plate/decidua basalis
Chorionic plate = fetal side
Decidua basalis = derived from endometrium - maternal side, containing maternal blood in lacunae
Function of placental membranes?
1) turnover of amniotic fluid (produced by amniotic cells and mainly derived from maternal blood)
2) enzymatic activity during initiation of labor.
Layers of placental membrane
Amnion (outer surface) → chorion → extravillous trophoblast → decidua capsularis
Amnion
single layer of flat, cuboidal or columnar epithelial cells derived from fetal ectoderm. Passively attached to chorion by amniotic fluid pressure.
Chorion
tough fibrous layer that carries fetal blood vessels, often with atrophied villous remains (chorion frondosum).
Fetal parenchyma:
-Fetal compartment is ________
-Maternal compartment is _______
Fetal compartment = INTRAvillous
Maternal compartment= INTERvillous
Fetal parenchyma can be infected with what bacteria?
**Listeria infection - cause of acute inflammation and abscess within placenta parenchyma
Gravida/Para nomenclature
G = NUMBER P = OUTCOME
→ TPAL = Term delivery, Preterm delivery, Abortion (< 20 weeks), Living children
Acute Chorioamnionitis
secondary to intra-amniotic infection with neutrophils in fetal membranes
occurs in 25% of live births, 67% preterm deliveries (> 20 weeks)
Poor correlation with clinical chorioamnionitis (Fever, leukocytosis, uterine tenderness, tachycardia) with histological chorioamnionitis
Typically due to group B strep
Can get fetal acute inflammation in response to maternal infection
Acute Chorioamnionitis
2 possible routes of infection
1) Ascending: bacterial from cervico-vaginal flora → maternal neutrophils in membranes
2) Transplacental (hematogenous) → chronic villitis
- TORCHES = Toxoplasma, Rubella, CMV, HIV/HSV, Syphilis
Bugs that can cause infectious villitis? (4)
1) Syphilis → perivascular fibrous proliferation
2) Toxoplasmosis → granulomatous with cysts
3) Herpes → multinucleated cells with inclusions
4) Listeria → acute inflammation destroying villi
Villitis of unknown etiology
Maternal infiltrate of lymphocytes that attack and destroy the villi
10-15% recur → ⅔ get IUFD
Meconium
NEVER normal before 36 weeks GA
Due to fetal stress vs. fetal maturity
→ toxic to baby, placenta, and vascular smooth muscle
Can result in aspiration pneumonia and myonecrosis
feto-maternal hemorrhage (FMH)
Represents a massive amount of fetal blood in maternal circulation (> 20%)
Can test for this with Kleihauer-Betke Test (tests for HbF)
Placental Infarct
acute cessation of maternal flow to live fetus
→ central more significant than peripheral
Placenta Accreta
placenta attaches to myometrium WITHOUT penetrating it
Most common time
Trophoblasts invade abnormally deeply → chorionic villi adhere to myometrium → postpartum hemorrhage
Risk with prior C-section, endometrial ablation, and multiple D&Cs
Placenta Increta
placenta villi INVADE into myometrium
Placenta Percreta
placenta villi PENETRATE through serosa (myometrium)
Placenta Previa
what is it?
how does it present?
placenta covers internal cervical os or lower uterine segment
Increased risk for abruption, postpartum hemorrhage, C-section
Associated with PAINLESS third trimester bleeding
How will placenta ccreta, increta, and percreta present?
Often detected on US prior to delivery
No separation of placenta after delivery –> postpartum bleeding –> can cause sheehan syndrome
Abruptio Placentae
what is it?
risk factors for it?
premature separation (partial or complete) of placenta from uterine wall before delivery of infant
SX: vaginal bleeding, abdominal/back pain, rapid uterine contractions
Can be chronic or acute
Causes fetal deprivation of oxygen and nutrients
Preeclampsia
HTN + proteinuria after 20 weeks gestational age
May proceed to eclampsia (+ seizures) and/or HELLP syndrome
Incidence increased in patients with preexisting HTN, diabetes, chronic renal disease, or autoimmune disorders
Presentation of placental abruption?
ABRUPT, PAINFUL bleeding (concealed or apparent) in third trimester
Possible DIC, maternal shock, fetal distress
Life threatening for mother and fetus
What causes preeclampsia?
Caused by abnormal placental spiral arteries (muscular, thick maternal endothelial cells NOT replaced by trophoblasts)
–> endothelial dysfunction, vasconstriction, ischemia
Spontaneous abortion:
causes in first, second and third trimesters?
First trimester - chromosomal (vast majority)
Second trimester - structural defects, placental, infectious
Third trimester - placental, structural defects
Intrauterine Growth Restriction (UGR)
if growth restircition is symmetric then…
If it is asymmetric, then…
Symmetric → genetic etiology
Asymmetric → relative macrocephaly, placental or maternal etiology, often oligohydramnios
Intrauterine fetal demise (IUFD) - what happens to hCG
hCG initially normal and then reduces when baby dies
Trisomy 21
47 (XX or XY) Small for gestational age Round/flat face with slanting palpebral fissures TRansverse palmar crease Heart (typically ASD) and GI anomalies Pancreatic or bone marrow fibrosis Increased risk of ALL and Alzheimer’s
Trisomy 13
Patau’s Syndrome, 47 XX or XY Small for gestational age Polydactyly and facial defects Cutis aplasia Heart (VSD) and brain defects (holoprosencephaly) Pancreatico-splenic fusion NORMAL quad screen early in gestation
Trisomy 18
Edward’s Syndrome, 47 XX or XY Small for gestational age Hand deformities, micrognathia Rocker bottom feet Heart anomalies, renal fusion Omphalocele
Triploidy
69XXX or 69XXy
Incompatible with life
Severe IUGR
Syndactyly (fusion of digits)
Fetal hydrops
abnormal fluid collection (edema) under skin, within abdomen or chest cavity - often polyhydramnios
Fetal hydrops
Immune vs. non-immune causes?
Immune: maternal ab against fetal RBCs cross placenta → hemolyzed in fetal spleen → severe anemia
Usually Rh antigens
Non-immune: infectious, cardiac, or other congenital anomalies
Acardiac twin
“Parasitic twin” fails to develop head, arms, and heart → gets blood from host twin → Host twin gets CHF because it is doing double work to perfuse both
Teratomas
where is the most common site in a newborn?
Sacrococcygeal: most common neoplasm of newborn
