Maternal Physiology Flashcards
Major hormones involved in regulating lactation
- Prolactin: Stimulates production of milk
- Progesterone: Interferes with prolactin signaling in breat alveolar cells, suppressing milk production
- Oxytocin: Stimulates lactation
Clinical “types” of gestational diabetes
A1: Diet controlled
A2: Requiring pharmacologic intervention
What abnormalities are infants born to patients with gestational diabetes at increased risk for?
Metabolic features of GDM that predispose to poor outcomes
Pregnancy is a ___-genic state
Pregnancy is a diabeto-genic state
As part of normal pregnancy physiology, fasting insulin levels increase and post-prandial blood glucose increases, while hepatic insulin sensitivity decreases.
Decreased insulin sensitivity is mediated by human placental lactogen, which is a strong anti-insulin hormone. Increased baseline insulin is mediated by estrogen and progesterone, which induce pancreatic beta islet cell hypertrophy.
Why does peripheral sensitivity to maternal insulin decrease in pregnancy?
Human placental lactogen from the placenta antagonizes its activity in these tissues
Screening for gestational diabetes
- If risk factors present, screen at first OB visit with 50g glucose tolerance test (1 hour, threshold >200 mg/dL)
- If no risk factors present, screen at 26-28 wks gestation with 50g glucose tolerance test (1 hour, threshold >140), and if this is positive, a confirmatory 100g glucose tolerance test (3 hours, threshold >140).
Treating GDM
- Behavioral:
- Diet
- Pharmacologic:
- 1st line: Insulin
- 2nd line: Metformin, glyburide with monitoring
Fetal complications of GDM
- Shoulder dystocia due to accumulation of fetal fat at shoulders
- Increased need for caesarean delivery
-
polyhydramnios (think of it as fetal polyuria)
- Increases risk for pre-term labor
Pre-term labor in GDM
- Traditionally, for pre-term labor we administer betamethasone in order to ensure sufficient surfactant production
- But. . . in patients with GDM this has the side effect of causing a glucose surge
- This necessitates close monitoring and potentially insulin therapy
- Effects can be seen up to 2 weeks following betamethasone administration
Neonatal metabolic consequences of GDM
- When the infant is born, it will have been accustomed to dealing with high levels of glucose by producing an excess of insulin
- When this supply is cut off, the infant will still be producing that insulin excess for ~24 hours, which may lead to:
- Neonatal hypoglycemia
- Hypercalcemia
- Hyperbilirubinemia
- Polycythemia
- Later on, they also are at increased risk for childhood obesity and adult type II diabetes
Maternal risks of GDM
-
Amenable to glucose control:
- All of the normal DM stuff
- Increased risk of need for caesarean delivery
- Risk of severe perineal laceration
-
Not amenable to glucose control:
- Pre-eclampsia
- Development of overt type II diabetes
Progesterone and blood pressure
Progesterone both promotes vasuclation of the placenta and relaxes vascular smooth muscle, leading to decreased blood pressure.
This reaches a nadir around the end of the 2nd trimester.
Six key hormones of pregnancy
Pregnancy wheel
Pathology that can be induced by elevated progesterone in pregnancy
- GERD (smooth muscle relaxation)
- Gallstones (inhibition of CCK)
- Constipation (decreased GI motility)
- N/V (along with beta hCG, morning sickness)
Hyperemesis gravidarum
- When the nausea and vomiting of pregnancy becomes truly pathologic
- Weight loss
- Ketonemia
- Metabolic alkalosis (similar physiology to bulemic metabolic alkalosis)
Three contributors to GERD during pregnancy
- Progesterone (decreased motility, smooth muscle relaxation)
- Relaxin (smooth muscle relaxation)
- Mass effect of enlarged uterus (pushes stomach up)
Rate of increased cardiac output in pregnancy
Slightly outpaces the rate of volume expansion in order to also cover the decreasing vascular resistance
Increases by about 25% by 8 weeks, 50% by the third trimester
In the first half of pregnancy, CO increases due to ___.
In the second half of pregnancy, CO increases due to ___.
In the first half of pregnancy, CO increases due to increased stroke volume.
In the second half of pregnancy, CO increases due to increased heart rate.
Supine postural hypotension syndrome
- The hypotension that pregnant women experience when lying flat on their backs
- Due to compression of the IVC by the womb
-
We advise pregnant women to not lay flat on their back while they are sleeping
- We recommend sleeping with a left tilt (IVC is on the right) or on their side
Respiratory changes during pregnancy
- Oxygen demand increases by 20%
- Minute ventilation increases by 30-40%
- Consequently, in order to meet this demand for oxygen, women must hyperventilate and blow of extra CO2
- This is the mechanism by which the physiologic alkalosis of pregnancy occurs
- It is balanced by kidney bicarbonate excretion
Lab features of the physiologic alkalosis of pregnancy
A fully compensated respiratory alkalosis with normal pH
Changes in the maternal thorax during pregnancy
- Diaphragm elevated by 4cm due to mass effect
- Chest diameter and circumference increase
Physiologic anemia of pregnancy
- Plasma volume increases by 45% by the third trimester
- RBC volume increases by 35% by the third trimester
- You do the math
- This makes the average Hb about 12.5 in the pregnant woman at term, compared to 14 in the non-pregnant woman
- Iron supplementation is given to help prevent further anemia
Maternal blood pressure starts to decline by week ___.
They reach a nadir and begin to rebound by around ___.
Maternal blood pressure starts to decline by week 7.
They reach a nadir and begin to rebound by around week 24-26.
Common cardiovascular exam findings in pregnancy
- Distended neck veins common due to physiologic increase in volume
- Systolic flow murmur common due to physiologic increase in CO and anemia
Maternal fetal circulation
- Three shunts of pregnancy (in order from umbilical vein):
- Ductus venosus
- Foramen ovale
- Ductus arteriosus
1000 foot view of pre-eclampsia and eclampsia
Four types of hypertension in pregnancy
- Chronic hypertension (Predates pregnancy or diagnosed pre-20 wk mark)
- Gestational hypertension (New onset post-20 wk mark, WITHOUT proteinuria OR end organ dysfunction)
- Pre-eclampsia (New onset post-20 wk mark, WITH proteinuria OR end organ dysfunction)
- Chronic hypertension with superimposed pre-eclampsia (Pre-existing chronic hypertension with NEW proteinuria OR end organ dysfunction starting post-20 wk mark)
Cytotrophoblast invasion of uterine spiral arteries
- A normal step in placental development
- Cytotrophoblasts enter uterine arteries and replace their endothelium through metaplasia
- Allow for conversion of high-resistance, small-diameter vessels to high-capacitance, low-resistance vessels
- This process is disordered in pregnant women who will eventually develop pre-eclampsia, such that the maternal endothelium is not replaced by cytrotrophoblasts.
Risk factors for pre-eclampsia
- History of pre-eclampsia
- Primiparity
- Pre-eclampsia in first degree relative
- Multiple gestation
- Maternal factors:
- HTN, kidney disease, diabetes, hypercoagulability, SLE, obesity, >40 years age
Diagnosing pre-eclampsia
Past what point are we no longer worried about pre-eclampsia for a given pregnancy?
37 wks gestational age
When should you treat pre-eclampsia with antihypertensives, and which antihypertensives should you use?
- When to treat: If BP exceeds 160 systolic OR 110 diastolic
- What to use:
- Nifedipine
- Labetalol
- Hydralazine
Managing pregnancy in patients with pre-eclampsia
- Ultrasound should be offered to assess for signs of restriction
- If evidence seen, umbilical artery dopplar velocimetry
- Monitor fetus biweekly
- Betamethasone administration prior to 34 weeks EGA
-
Induce labor at 37 weeks EGA
- If pre-eclampsia with severe features, induce labor at 34 weeks EGA or sooner if worsening symptoms
- Magnesium sulfate for seizure PPX
- Caesarean section not necessarily required
Treatment of eclamptic seizures
- Magnesium sulfate IV
- Once patient is stabilized, delivery should begin
- C section not necessarily required
Eclamptic seizures may occur. . .
. . . before, during, or after delivery
HELLP stands for. . .
. . . hemolysis, elevated liver enzymes, and low platelets
Features of HELLP syndrome clinical presentation
- Woman in third trimester of pregnancy
- Likely with pre-eclampsia or eclampsia
- Epigastric pain, malaise, nausea, and headaches
HELLP may progress to. . .
. . . DIC
sFlt1 theory of pre-eclampsia
Magnesium toxicity
For a patient with chronic hypertension, will treating their hypertension reduce their risk of developing pre-eclampsia?
No
And it makes sense if you think about the mechanism. Pre-eclampsia is more of an anatomical problem with the vascular system than typical hypertension, and its systemic mediators are completely different.
Methyldopa
- Often used for management of chronic hypertension in pregnancy
- Centrally stimulates alpha 2 adrenergic receptors
What antihypertensives cannot be used in pregnancy?
- ACE inhibitors
- ARBs
- Mineralocorticoid antagonists
In a pregnant patient in their third trimester with chronic hypertension and superimposed pre-eclampsia, what is the #1 absolute contraindication to magnesium?
Mysathenia gravis
Excess magnesium will block intracellular calcium influx, worsening muscle weakness and precipitating resipiratory failure
Recommended weight gain for pregnant patient by BMI
- Underweight (BMI < 18.5): Gain 28-40 lbs
- Normal weight (BMI 18.5-24.9): Gain 25-35 lbs
- Overweight (BMI 24.9-29.9): Gain 15-25 lbs
- Obese (BMI > 30): Gain 11-20 lbs
A patient arrives for prenatal counciling. Their brother has sickle cell anemia, but neither of their parents do. Their partner is from an ethnic group with a 1/10 prevalence of carrier status. What is the probability of their child having sickle cell disease?
Probability that the patient is a carrier: 2/3 (since we know we can elimiate the possibility of her having sickle cell disease)
Probability that the partner is a carrier: 1/10
Probability that the child of two carriers will have the disease: 1/4
2/3 x 1/10 x 1/4 = 2/120 = 1/60
Prophylaxis against the development of pre-eclampsia in pregnancy (not eclapmsia)
In a patient who is high-risk for pre-eclampsia, low-dose aspirin started between weeks 12 and 28 eGA and continued until delivery has been shown to reduce incidence of pre-eclampsia
Female HPG axis
Therapy for cervical insufficiency with risk of pre-term delivery or inevitable abortion
- Rule out labor and inevitable abortion by transvaginal ultrasound and manometry to measure for contractions
- Rule out infection with amniocentesis
- Cerclage stitch placement and cervical pessary
Another name for dyspnea of pregnancy
Progesterone-induced hyperventilation
This one also helps remind you that progesterone is the main driver and has an effect on the central controller as well as the smooth muscle.
However, it does not effect the compliance of the lung.
Definition of anemia in pregnany
Hb less than 10.5 g/dL in a pregnant individual
The acini of the breast are not fully differentiated until . . .
. . . term pregnancy
Five mechanisms involved in complete breats milk production
- Exocytosis: Delivers lactose to the lobular lumen, and also drives water into the lumen through osmosis
- Reverse pinocytosis: Delivers lipids and phospholipids to the lobular lumen from the smooth ER
- Transcytosis: Delivery of IgA, albumin, and hormones to breast milk by deliverying from basolateral to apical surface of lobular cells
- Apical transport: Delivers sodium and potassium into the lobular lumen
- Paracellular movement: Allows movement of immune cells and other materials across lobular cell-lobular cell tight junctions
If breast milk is not emptied. . .
. . . there will eventually be a reduction and involution of mammary glands.
This is through a mechanism of increased pressure in mammary gland lobules, which is sensed by the cells and reduces their responsiveness to prolactin and oxytocin, as well as inhibiting tight junction transit. Sensitivity to prolactin is reduced by feedback inhibitor of lactation (FIL), which is secreted apically into lobules and causes a downregulation of prolactin receptors on mammary gland cells.
Why does suckling cause cramps in some women?
Because of oxytocin! Oxytocin happens to be responsible for both uterine contractions (it shares this role with prostaglandin F2a) and breast milk ejection.
Etiologies of delayed mature milk production in the postpartum period
- Cesarean delivery
- Primiparous women
- Placental retention
- Diabetes
- Stressful parturition
What is absent or low in breast milk?
Vitamin K is notably absent
Iron and Vitamin D are notably present only in small quantities.
We supplement all three of these things in neonates.
Effects of estrogen and progesterone on breast tissue
- Estrogen induces lobule growth
- Progesterone induces alveolar hypertrophy
For the first few weeks of life, a baby should feed ___ times per day
For the first few weeks of life, a baby should feed 8-12 times per day
Or, every 2-3 hours
By day 5 of life, a baby should make ___ wet diapers per day and ___ stools per day
By day 5 of life, a baby should make 6-8 wet diapers per day and 3-5 stools per day
Therapy for breast engorgement
Acutally. . . keep breastfeeding!
Breastfeeding will help shorten the duration of symptoms. Over-the-counter analgesics like ibuprofen and tylenol are also recommended.
Galactocele
Fancy word for plugged lactiferous duct.
This is the most common cause of mastitis, since backed-up milk is such an excellent growth medium for bacteria
Therapy for mastitis
1st line: Dicloxacillin and continued breastfeeding or pumping
2nd line: Erythromycin, clindamycin and continued breastfeeding or pumping
Methicillin-sensitive Staph aureus is the most common etiology. It is important to emphasize that women can and should continue to breastfeed despite having mastitis, and that their infant is not at risk of infection from mastitic breast milk. The continual forward flow will both help unclog involved ducts and prevent superimposed engorgement, having therapeutic benefit.
Syndrome of breastfeeding mother with itchy areola and infant with white plaques in its orophaynx
Candida!!!
This is a common presentation. Both mom and baby should be treated with antifungals.
What to advise if your patient says “I am planning on using formula to feed my baby until my milk comes in”
There are a few problems with this:
- Milk will not come in unless a woman is actively breastfeeding
- Colostrum, while not milk, is beneficial in its own right for newborns and is usually present by PPD#2.
Contraindications to breast feeding
- Infectious: Hepatitis B, HIV, Tuberculosis, or active herpetic lesion on the breast
- Galactosemia: Infants with galactosemia should NOT be breastfed. They have one of the two common defects in galactose metabolism. Lactose consumption may cause hepatitis or osmotic diuresis, both of which are life threatening for neonates.
Tocolysis and corticosteroids in twin pregnanices
They are avoided in all pre-term multiple gestation pregnancies due to the risk of pulmonary edema in mom.
Intrahepatic cholestasis of pregnancy
- Presents as generalized pruritis without signs of atopy, jaundice, or skin lesions
- Usually begins in the third trimester
- Caused by mildly elevated levels of circulating bile acids, which can be measured on laboratory testing.
- However, the diagnosis itself is clinical
- Must be distinguished from true cholelithiasis, cholechstitis, or hepatitis, which will be associated with markedly elevated bile acids.
- Associated with increased incidence of prematurity, fetal distress, and fetal loss
- 1st line: Antihistamines, cornstarch baths, delivery at 37 weeks
- 2nd line: Ursodeoxycholic acid
- 3rd line: Naltrexone or Cholestyramine
Pruritic Urticarial Papules and Plaques of Pregnancy (PUPPP)
- Unknown etiology
- Unique to pregnancy
- Intense pruritis and erythematous papules beginning on the abdomen and spreading to extremities
- IF is negative for IgG and complement (distinguishing from Herpes gestationis)
- Unlike other pruritic diseases of pregnancy, PUPPP is not associated with higher rates of morbidity and mortality in the pregnancy.
- Treat w/ topical steroids and antihistamines.
- Once treated, it typically will not recur. It is confined to a single episode, usually ~35 weeks.
Herpes Gestationis
- No relationship to Herpes viridae
- aka Pemphigoid gestationis
- Pruritic, bullous disease of skin that can occur during pregnancy
- Usually begins in 2nd trimester
- Caused by IgG against basement membrane proteins and associated complement activation
- Diagnosis confirmed by immunohistochemistry
- May be associated with transient neonatal Herpes gestationis at birth due to IgG transfer
- Increased incidence of fetal growth restriction and stillbirth
- Treat w/ corticosteroids
Acute Fatty Liver of Pregnancy
- Acute microsteatosis of the liver thought to be due to mitochondrial dysfunction in beta oxidation of fatty acids
- Affected women are heterozygous for long chain 3-hydroxyacyl-coenzyme A Dehydrogenase (LCHAD)
- Presents as acute RUQ pain, malaise, N/V, acute renal failure, hypoglycemia, coaguloptahy, and acute fulminant liver failure
- Hypoglycemia is a very prominent and unique feature. It will often be quite refractory, as fundamentally this is a disease of fat metabolism, so glucose is rapidly utilized in its place.
- Delivery is the only treatment and must be performed immediately once the diagnosis is made
D dimer in pregnancy
Elevated at baseline, NOT useful in the assessment for likelihood of pulmonary embolism
Peripartum cardiomyopathy
- Treat w/ diuresis and inotropes
Most common side effect of long term heparin therapy in pregnancy
Osteoporosis
Mechanism for this is thought to be stimulation of osteoclast activity and reduction in osteoblast activity, but how this occurs is not known
Most common cause of maternal death in eclampsia
Intracerebral hemorrhage
Greatest risk is just prior to delivery and within the first 24 hours postpartum
When to treat hypertension in pre-eclampsia
Only severe-range hypertension (over 160/110) is treated in pre-eclampsia.
Otherwise, even if the patient is hypertensive to 150s/100’s, we do not treat.
First and second signs of magnesium toxicity
- Loss of deep tendon reflexes
- Dyspnea due to pulmonary edema
Treating Grave’s in pregnancy
- If the patient wishes to retain their thyroid, treatment is principally with propylthiouracil
- Additional propylthiouracil, corticosteroids, and propranolol may be used to treat exacerbations / thyroid storm
- Note that propylthiouracil rarely causes bone marrow aplasia, which may lead to leukopenia and sepsis
- The reason methimazole is contraindicated is due to associations with aplasia cutis (skin and scalp defects)
- Thyroidectomy is resserved for patients who cannot tolerate or adhere to medical therapy
Hyponatremia and hypoosmolality of pregnancy
A centrally-driven process due to increase in vasopressin levels secondary to the “reset osmostat phenomenon”.
At the same time, vasopressinase expressed by the placenta serves to decrease levels of vasopressin peripherally by reducing its half-life, providing a counter-effect.
HTN and pregnancy
Patients with medically controlled chronic HTN are at elevated risk of new pre-eclampsia close to term, and so controlled chronic HTN is an indication for induction at 38-39 weeks.
Uncontrolled chronic HTN is at even higher risk, and so late-preterm induction at 36-37 weeks is indicated.
When should you deliver a fetus in a mother with ICP?
36-37 weeks or at the time of diagnosis if beyond this point
This is because it is associated with poor fetal outcomes and third trimester or term prengancy loss. The exact pathologic mechanism is not known.
Is maternal DKA an indication for delivery?
NO
Even though the fetus will likely display heart rate abnormalities, you should not deliver, since these will almost always correct with treatment of the DKA.
You should only deliver if the abnormalities do NOT correct with treatment of DKA.
Risk of congenital defects for infants delivered by “true” gestational diabetics
Since gestational diabetes trypically does not cause a substantial elevation in blood glucose until ~2nd term, blood glucose levels are relatively normal during organogenesis, which is the time when these anomalies first develop.
So, if an individual has “true” gestational diabetes, their rate of congenital anomalies is approximately the same as that of the general population.
For the same reason, true diabetics with tightly-controlled blood glucose and an A1c < 7% at the beginning of their pregnancy are not at increased risk either.
TSH and prolactin
When a patient is hypothyroid, TSH elevation can cause a mild hyperprolactinemia.
However, hyperprolactinemia does not suppress TSH, and cannot lead to hypothyroidism.
