OB lecture 2: endocrinology

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What are the major hormones of pregnancy?

hCG (human chorionic gonadotropin)
hCS (human chorionic somatomammotropin) aka human placental lactogen
Prolactin
Progesterone
Estrogen

hCG is a glycoprotein with alpha and beta subunits. Which subunit is used in testing?

Beta.

What is the source of hCG?

1. normal placental tissue (early as 6-8 days postconception) including multiple placental development (multiple gestation)
2. hydiatidiform moles (molar pregnancy)
3. choriocarcinoma cells (malignant trophoblastic cells)
4. ectopic pregnancies

What is the normal rise and peak of hCG?

Rapid rise at 8th day and peaks at 80 days

What is the major role of hCG?

to stimulate progesterone production by corpus luteum. hCG stims Leydig cells of male fetus to produce testosterone.

What do low levels of hCG in early pregnancy suggest?

poor placental function and may predict abortion or ectopic pregnancy

What do high levels of hCG in early pregnancy suggest?

Very high values suggest multiple gestation or trophoblastic neoplasia

What produces Human Chorionic Somatomammotropin (hCS)/Human Placental Lactogen (HPL)?

Formed by placenta. Found in normal and molar pregnancies.

When is hCS/HPL detectable?

the 6th week until delivery

What is the function of hCS/HPL?

1.Increases fatty acids to provide a source of energy for maternal metabolism and fetal nutrition (promotes lipolysis)

2.Anti-insulin action of HPL -works by reducing insulin affinity to insulin receptors, which increases maternal levels of insulin leading to protein synthesis and prolongs elevated blood glucose. This mobilizes a source of amino acids for transport to fetus. Therefore shifts glucose availability toward fetus.

Where is prolactin made?

Anterior lobe of maternal pituitary gland, anterior lobe of fetal pituitary gland, decidual tissue of uterus

What is the prolactin value in a non-pregnant female?

8-25 ng/mL

What is the significance of prolactin?

Prepares mammary glands for lactation

What does relaxin do?

Softens and dilates the cervix and relaxes the symphysis pubis and pelvic joints in pregnancy. It inhibits uterine contractions

Which two prostaglandins cause uterine contraction?

PGE2 and PGFalpha

During pregnancy, what is the source of progesterone?

Pregnant state-produced by corpus luteum (until 7th-8th week) then placenta assumes production until parturition.

What are the 6 functions of progesterone during pregnancy?

1.Prepares endometrium for nidation
2. Maintains the endometrium.
3. Relaxes the myometrium.
4. Prevents uterus from contracting
5. Has natriuretic actions during pregnancy, probably by blocking action of aldosterone on kidney
6. Precursor for critical fetal hormones during pregnancy (corticosteroids and testosterone)

What are the 3 forms of estrogen?

1. Estrone-relatively weak
2. Estradiol-most potent
3. Estriol-very weak. Produced in very large quantities during pregnancy (90% of all estrogens during preg.)

*Extremely low levels or no estriol associated with:

1. fetal demise
2. anencephaly
3. maternal ingestion of corticosteroids
4. congenital adrenal hypoplasia
5. Placental deficiency

*Decline in estriol or failure of estriol to rise associated with:

1. maternal renal disease
2. hypertensive disease during pregnancy
3. preeclampsia and eclampsia
4. intrauterine growth retardation (IUGR)
*Large quantities of estriol produced with multiple gestation and as a result of Rh isoimmunization.

What are the 6 presumptive symptoms of pregnancy?

1. Amenorrhea
2. Breast changes
3. Nausea +/- vomiting
4. Frequent urination
5. Fatigue
6. Quickening

hyperemesis gravidarum is:

Excessive n/v associated with pregnancy. Very serious.

What is the pharmacological treatment of hyperemesis gravidarum?

pyridoxine (B6) and doxylamine; phenothiazines (prochlorperazine, chlorpromazine, promethazine);
Ondansetron (Zofran)

What are the clinical signs of pregnancy?

1. Enlargement of the abdomen
2. Uterine and cervical changes
3. Endocrinological changes

What is Hegar's sign?

softening between uterus and cervix-feels like two separate structures.

What is Chadwick's sign?

bluish color of cervix in first 6-8 weeks pregnancy due to congestion of pelvic vasculature.

What is leukorrhea?

increased vaginal discharge of epithelial cells and cervical mucus due to hormone stimulation

What is Goodell's sign?

cyanosis and softening of cervix due to increased vascularity of cervical tissue as early as 4 weeks.

What is Landin's sign?

around 6 weeks the uterus softens in anterior midline along uterocervical junction.

What is McDonald's sign?

uterus becomes flexible at uterocervical junction at 7-8 weeks

What is Von Fernwald's sign?

irregular softening of fundus over site of implantation at 4-5 weeks

When do Braxton-Hicks contractions begin?

28 weeks

How is pregnancy diagnosed/confirmed?

1. Fetal heart beat (8 weeks)
2. US (gestational ring, embryo)

What complications can occur in the second trimester?

1. Premature rupture of membranes (PROM)
2. Premature labor
Both usually from incompetent cervix

What is the fetal weight gain during the last 4 weeks of pregnancy?

0.5lb/week

Heavy bleeding in the 3rd trimester can be due to:

: placenta previa or abruptio placentae (premature separation of placenta)

What are the most common types of back pain during pregnancy and what are their causes?

1. Posterior pelvic pain-not experienced before pregnancy; related to pelvic insufficiency, pelvic relaxation syndrome and sacroiliac syndrome. Often associated with pubic symphysis pain.
2. Lumbar pain-Felt over lumbar spine and muscles. Not felt in sacral area; may radiate to thigh, leg or foot.

How should you manage back pain in pregnancy?

Avoid fatigue, lifting with twisting
Avoid sustained postures
Use lumbar support and foot stool while sitting
Aquatic exercise in cool water
Extension exercises
Local application of heat (non-electric); avoid sauna/hot tub
Limited meds-avoid NSAIDS and muscle relaxants; Tylenol ok

How much weight should a woman with a normal BMI and a singleton gain?

25-35lbs
• 1/2 lb/wk for 28 weeks
• 1 lb/wk after 28 weeks

How much weight should an underweight teen with a singleton gain?

28-40lbs or 5lbs every 4 weeks in the second half of pregnancy

How much weight should an obese female with a singleton gain?

15lbs, not to exceed 25lbs

A normal fetus weighs what when?

26-28 weeks-1000 g (over 2 lb)
36 weeks-2500 g (5.5 lb)
40 weeks-3300 g (7-7.5 lb) gain ½ lb a week

What cells secrete surfactant?

type II pneumocytes of fetal lung alveoli

How is the risk of respiratory distress in newborns determined?

Using the lecithin to sphingomyelin (L/S) ratio.
-Before 34 weeks, the L/S ratio is one (1), then L>S.
-L/S ratio greater than 2 - low risk of respiratory distress
-L/S ratio less than 2 - increased risk of respiratory distress
-L/S ratio of 1.5 to 2.0 - respiratory distress (40%)
-L/S ratio less than 1.5  respiratory distress in 73% (fatal in 14%)
*Presence of phosphatidylglycerol shows lung maturity and is a good sign.

What is the lie of the fetus?

Relation of long axis of fetus to the long axis of the mother (longitudinal or transverse)
1. Longitudinal lie-99% of labors. Head up or down.
2. Transverse lie-fetus crosswise in uterus.
3. Oblique lie-unstable situation, becomes either longitudinal or transverse.

What are the 3 types of cephalic presentation?

Position of fetal head in relationship to body of fetus.
a. Vertex-head flexed; chin in contact with chest; occiput of fetal head presents. Occurs 95% time.
b. Face-neck extended; occiput and back of fetus touching; face presenting part.
c. Brow-fetal head partially extended; converts into vertex or face during labor.

What are the 3 types of breech presentation?

Position of legs and buttocks, which present first. Occur 3.5% time.
a. Frank breech-thighs flexed, legs extended
b. Complete breech-legs flexed on thighs, thighs flexed on abdomen.
c. Footling breech-one or both feet or knees present.

What is the puerperium?

The period 4-6 weeks immediately after delivery to the time reproductive tract returns to non-pregnant condition. It involves:
1. Involutionof the uterus
2. After pains
3. Lochia
4. Diuresis
5. Leukocytosis and changes in blood volume
6. Menstruation

What is the lochia?

Lochia: Uterine discharge that follows delivery and lasts 3-4 weeks.
Foul-smelling lochia think infection.
Types of Lochia:
a. Lochia rubra-blood-stained fluid; lasts first few days
b. Lochia serosa-3-4 days after delivery; paler than lochia rubra, mixed with serum
c. Lochia alba-after 10th day; mixed with WBC's; yellow-white color.

How is postpartum hemorrhage defined?

*Blood loss in excess of 500 ml during the first 24 hours after delivery.
Causes:
1. Trauma to genital tract (episiotomy, lacerations of cervix, vagina or perineum, rupture of uterus)
2. Failure of compression of blood vessels at the implantation site (hypotonic myometrium, retention of placental tissue (placenta accreta)
3. Coagulation defects-congenital or acquired (hypofibrinogenemia, thrombocytopenia)

How is postpartum hemorrhage managed?

1. Vigorous massage of uterine fundus.
2. Uterine contracting agents (oxytocin/pitosin)
3. Manual exploration of uterine cavity for retained placenta or uterine rupture
4. Inspection of cervix and vagina for lacerations
5. Curettage of uterine cavity
6. Hypogastric artery ligation, embolization of uterine vessels and rarely, hysterectomy.

How is puerperal infection defined?

*Any infection of genital tract during the puerperium accompanied by temp of 100.4F (38C) or higher that occurs for at least 2 of the first 10 days postpartum, exclusive of first 24 hours. Prolonged rupture of membranes and multiple vaginal exams can cause infection.

What are the 3 types of pelvic infections?

1. Endometritis (childbed fever)-Most common. Involves endometrium and myometrium. Usually polymicrobial.
2. Parametritis-Retroperitoneal pelvic connective tissue
3. Thrombophlebitis-Puerperal infection that extends to pelvic veins.

How is puerperal infection managed?

*CULTURE urine, endometrial cavity tissue and blood to determine site.
*Antibiotics-Start with broad-spectrum and then switch when C&S returns.
*Give heparin when thrombophlebitis suspected and high temps don't respond to antibiotics.

What are the risk factors for puerperal infection?

1. Mode of delivery
2. Rupture of membranes; PROM
3. Duration of labor
4. Multiple digital exams
5. Internal uterine monitoring
6. Other-endogenous bacterial colonization, poor nutrition, poor hygiene, age, trauma

Signs and symptoms of endometritis:

1. Fever
2. Tachycardia
3. Uterine tenderness
4. Foul-smelling lochia
5. Malaise
6. Ileus

DDx of endometritis:

1. Atelectasis
2. Drug fever
3. Endocarditis
4. Mastitis
5. DVT
6. UTI
7. Wound abscess
8. Thrombophlebitis

Treatment for endometritis:

1. Prevent infection
2. Prophylactic antibiotics in the peri-operative period (single dose Cefoxitin or Clindamycin and Gentamicin or Amp/sulbactam or Ticarcillin/clavulanate etc)

What hormones are involved in lactation?

*Progesterone, estrogen, placental lactogen, prolactin, cortisol and insulin stimulate growth and development of lactation.
*Prolactin stimulates milk production.
Initiation of lactation from delivery of placenta leading to decrease of estrogen and progesterone and increase in prolactin.
*Continuation of prolactin production from constant stimulation of breast (infant suckling). The more the mother breast feeds, the more milk she will produce.
*Oxytocin-let-down reflex to release milk. Stimulation of nipples during nursing increases oxytocin release.

What are the components of breast milk?

7% carbohydrate as lactose
3-5% fat
0.9% protein
0.2% mineral constituents as ash
Energy content 60-75% kcal/dl

What are the protein components of breast milk?

Casein
Alpha-lactalbumin
Lactoferrin
IgA
Lysozyme
Albumin

What is colostrum?

Pre-milk secretion. "Starter food". Yellowish, alkaline.Higher protein, vitamin A, immunoglobulin, sodium, chloride content than milk. Low carbohydrate, potassium, fat content. Provides immunity/antibodies, lymphocytes; has natural laxative action.

What is the immunological significance of human milk?

1. prophylactic value against infections.
2.bifidus factor (a carbohydrate) that supports the growth of Lactobicillus bifidus. L. bifidus inhibits growth of Shigella and E. coli and yeast.
3. protection against Staph infections.
4. Interferon in milk may provide a non-specific anti-infection factor.
5. Human milk probably has prophylactic value in childhood food allergies.
6. Secretory IgA in colostrum and breast milk decreases absorption of foreign macromolecules.

What are the disadvantages/contraindications of breast feeding for mom?

1. Restricts activities
2. Inconvenience
3. Very difficult with multiple births (twins etc)
4. Nipple tenderness and mastitis
5. Lowered bone mineral content of lumbar spine 6 months post-partum
6. Breast Cancer-absolute contraindication
7. Hypothyroidism-not suggested due to difficulty in Ca++ replacement
8. Augmentation mammoplasty with silicone implants-not a problem but any surgery involving nipple autotransplantation --> precludes nursing.

What are the disadvantages/contraindications of breast feeding for baby?

1. Breast cancer of mom
2. Active pulmonary TB in mom
3. Severe mastitis
4. Mom on chemotherapy
5. Mom HIV positive
Disadvantages for Infant:
1. Small number develop elevated bili (unconjugated) due to glucoronyl transferase
2. Weak, ill, very premature infants or cleft palate, choanal atresia or PKU babies
3. CMV transmission by mom

How many calories are needed by a lactating mom?

2000-2300

What is the average milk production?

120-180mL per feeding after 10-14 days

How can a mom tell if her baby is getting enough to eat?

*Baby's behavior and sleep periods and character of stool are best measures of success of feeding.
*Supplemental feeding of formula should be reserved for baby who doesn't gain weight because of not getting enough food.

What are the disorders/ complications of lactation?

1. Painful nipples
2. Engorgement
3. Mastitis
4. Galactocele
5. Rejection by baby
6. Fatigue

What is mastitis?

*Parenchymatous inflammation of mammary glands which may occur during lactation.
*Symptoms-engorgement of breasts, temperature, chills and a hard, red tender area on breast.
*S. aureus most common organism (from infant's nose and throat).

What is the treatment for mastitis?

a. Gram-positive antibiotic-Penicillin, Amoxicillin erythromycin for PCN allergic
b. Heat to breast
c. Nursing from affected breast to decrease engorgement but start on unaffected side to stimulate "let-down"
d. I & D if abscess develops and is suppurative

What is a galactocele?

Milk retention cyst. Caused by blockage of milk duct. Gradual onset. Usually unilateral.
Localized swelling or pain. Otherwise feels well. No fever.
Diagnosis by mammography.
Treatment is surgical removal or aspiration of cyst.

What are the considerations of drugs in breast milk?

*Weigh risk/benefit ratio.
In general, if necessary, give drug right after nursing--> lower concentration of substance in milk at next feed.
Single dose drugs should be taken just prior to infant's longest sleep period.
*Most drugs excreted in low concentrations in milk.
Water soluble drugs excreted in high concentration in colostrum.
Lipid-soluble drugs excreted in high concentration into breast milk.

How can lactation be inhibited?

1. Oldest and simplest method is to:
• Stop nursing
• Avoid nipple stimulation
• Refrain from expressing or pumping milk
• Bind breasts snugly for 48-72 hours.
• Ice bags and analgesics help.
Complaints: pain, breast engorgement and leaky breasts; resolve in approx. 2-3 days.

2. Estrogens +/- Androgens
Example: Clomiphene 100 mg QD x 5 days --> decreased prolactin secretion.
Complications: Increased incidence of venous thromboembolism.

3. Bromocriptine (Parlodel)
Inhibits prolactin secretion. Safe. Highly effective.
Example dose: 2.5 mg bid x 3 weeks.
Complications: nasal congestion, mild constipation, nausea, headache, dizziness, postural hypotension.

4. Oral Prostaglandin E2:
New. Inhibits milk secretion and breast engorgement.

*Presence of ? shows lung maturity and is a good sign.

phosphatidylglycerol

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