Quiz 10: Biomedical Sciences (Anderson - Pregnancy+Lactation and Hep Viruses)

What hormones are produced by the corpus luteum during the luteal phase?

estrogen and progesterone

What is the role of estrogen and progesterone during the luteal phase?

prepare and maintain the endometrium for implantation

What rescues the corpus luteum during pregnancy?

human chorionic gonadotropin (hCG) from the blastocyst/placenta

Why is hCG important early in pregnancy?

maintains progesterone and estrogen production until the placenta takes over

When does the morula stage occur?

at the 12-16 cell stage

When does a blastocyst form?

at ~50-60 blastomeres

Where does early embryo development occur before implantation?

during transit through the uterine tube to the uterus

What major event occurs during implantation?

maternal blood-filled lacunae intercommunicate around the implanted blastocyst

What begins forming around the primitive yolk sac during implantation?

extraembryonic endoderm

What is the function of decidual layers?

separate fetal tissue from maternal tissue

What substances freely pass across the placental barrier?

nutrients, O₂, CO₂, and waste products

What are the two fetal tissue layers surrounding the embryo?

amnion and chorion

What is the role of the amnion and chorion?

amnion secretes amniotic fluid; chorion forms the fetal placenta

What maternal tissue forms the maternal portion of the placenta?

decidua

What is the major function of the placenta?

exchange gases, nutrients, growth factors, and waste

Do maternal and fetal blood directly mix?

No

How does maternal blood interact with chorionic villi?

maternal blood flows through intervillous spaces around the villi for exchange

Which fetal vessels carry oxygenated vs deoxygenated blood?

umbilical arteries = deoxygenated; umbilical vein = oxygenated

Why are chorionic villi important?

provide massive surface area for placental exchange

What are the characteristics and functions of hCG?

placental peptide hormone, pregnancy marker, rescues corpus luteum progesterone production

What are the functions of human placental lactogen (hPL)?

alters maternal metabolism (lipolysis/glucose metabolism) and supports fetal angiogenesis

What is CRH involved in during pregnancy?

timing of parturition (birth)

What are progesterone's major roles in pregnancy?

prevents endometrial shedding and uterine contractions

When does placental progesterone production begin?

after ~6 weeks gestation

What are estrogen's major roles during pregnancy?

uterine growth, breast development, and stimulation of contractions near term

What tissue becomes a major endocrine organ during pregnancy?

placenta

What tissue synthesizes estrogens during pregnancy?

placental syncytiotrophoblasts

Where do placental estrogen precursors come from?

fetal adrenal gland, fetal liver, placenta, and maternal tissues

What does DHEAS stand for?

dehydroepiandrosterone sulfate

Why is timing of drug exposure important during pregnancy?

drugs can damage fetal structures undergoing rapid development at exposure time

What physicochemical property most favors placental crossing?

lipid solubility

How does molecular weight affect placental transfer?

MW 250-500 crosses easily; MW >1000 crosses poorly

Why do ionized drugs poorly cross the placenta?

charged drugs require transporters to cross membranes

How does protein binding affect fetal drug exposure?

free drug crosses more readily than protein-bound drug

What pregnancy-related factors affect fetal drug exposure besides drug properties?

amount reaching fetus, duration, tissue distribution, metabolism, transport rate, and developmental stage

What tissues significantly metabolize drugs during pregnancy?

placenta and fetal liver

What is the purpose of placental influx and efflux transporters?

bring nutrients in and keep toxicants/drugs out

What determines whether maternal drugs access fetal tissue?

drug physicochemical properties and transporter expression

Why can maternal drug responses change during pregnancy?

altered endocrine and physiologic states affect tissue responses

What maternal physiologic changes can alter drug effects?

changes in cardiac output and renal blood flow

Examples of predictable fetal drug toxicity.

opioid dependence, tetracycline tooth defects, thalidomide teratogenicity

Which fetal systems remain vulnerable for long periods during development?

CNS and external genitalia

What fetal toxicity is associated with tetracycline?

tooth staining during mineralization

What reproductive system changes occur during pregnancy?

uterus enlarges, cervix forms mucus plug, ovaries enlarge, vagina becomes more distensible

What is the role of the cervical mucus plug?

prevent microbial entry

How does the vagina adapt during pregnancy?

thickened lining, less connective tissue, more muscle tissue

What cardiovascular parameters increase during pregnancy?

blood volume, cardiac output, stroke volume, and heart rate

How does renal function change during pregnancy?

increased glomerular filtration rate and creatinine clearance

What contributes to increased GFR during pregnancy?

decreased renal vascular resistance

What are key breast anatomy and pregnancy-related changes important for lactation?

breasts contain lobes/lobules with alveoli producing milk; lactiferous ducts carry milk to nipple; estrogen causes duct/lobule proliferation during puberty and pregnancy

How does breast tissue appear before puberty?

mostly connective tissue with a few ducts

What effects does estrogen have on the breast during puberty?

stimulates duct branching, lobule/alveoli formation, and fat/connective tissue growth

How do menstrual hormones affect the breast?

fluctuating estrogen/progesterone alter fluid levels, circulation, and duct proliferation

What major breast changes occur during pregnancy?

significant duct proliferation and increased lobules/alveoli for milk production

What breast structures produce milk?

alveoli

Why are alveoli important pharmacologically?

drugs must cross the blood-milk barrier to enter milk within alveoli

What hormone primarily stimulates milk production?

prolactin

What hormone stimulates milk letdown/ejection?

oxytocin

What triggers oxytocin release during breastfeeding?

sensory stimulation of the nipple

Milk Let down Reflex Pathway

nipple stimulation → hypothalamus/posterior pituitary → oxytocin release → myoepithelial contraction → milk ejection

What major components are present in breast milk?

lipids, proteins, carbohydrates, vitamins, antibodies, and water

Why is breast milk important immunologically?

contains antibodies and immune-supportive factors for the infant

What cells synthesize milk in the lactating mammary gland?

alveolar epithelial cells

What physiologic changes support milk synthesis during lactation?

↑ blood flow, nutrient availability, protein synthesis, lipogenesis, and lactose synthesi

What forms the blood-milk barrier in alveoli?

tight junctions between alveolar cells

What pathways move substances into milk?

exocytosis/secretory pathways, transcellular transport, paracellular pathways, and transport proteins/channels

What substances are secreted into milk by alveolar cells?

proteins, lipids, sugars, salts, vitamins, minerals, antibodies, and nutrients

Are most maternal drugs detectable in breast milk?

Yes, but concentrations are usually low

What factors determine how much drug enters milk?

lipid solubility, transport mechanism, ionization, protein binding, molecular weight, and plasma concentration

How can nursing timing reduce infant drug exposure?

taking drugs 3-4 hours before nursing lowers circulating drug levels during feeding

What drug properties increase transfer/accumulation in breast milk?

low MW, weak bases, high lipid solubility, long half-life, and low protein binding

How do tight junctions affect drug entry into milk?

tight junctions help keep toxicants and many drugs out of milk; contamination depends on permeability and transport proteins

What are the major physiologic functions of the liver?

1. removes toxins/drugs

2. metabolizes nutrients

3. produces bile

4. breaks down bilirubin

5. produces cholesterol

6. converts ammonia to urea

Why is liver dysfunction dangerous during hepatitis?

the liver is essential for detoxification, metabolism, bile production, clotting factors, and vitamin storage

Which hepatitis viruses are RNA vs DNA viruses?

HAV, HCV, and HDV are RNA viruses; HBV is a DNA virus

What are the pre-icteric vs icteric symptoms of hepatitis?

pre-icteric = malaise, anorexia, nausea (IFN-mediated)

icteric = jaundice, dark urine, RUQ pain

Are hepatitis viruses directly cytopathic?

No, immune-mediated inflammation damages hepatocytes

What is fulminant viral hepatitis?

massive liver necrosis leading to liver failure and possible death

What causes jaundice in hepatitis?

incomplete elimination of bilirubin by the damaged liver

What are clinical signs of bilirubinemia?

yellow skin/sclera and tea-colored urine

How is bilirubin normally formed and eliminated?

heme from old RBCs → broken down to bilirubin → kidney conversion to urobilin → elimination in bile/feces or urine

Why does bilirubin accumulate during viral hepatitis?

damaged hepatocytes cannot properly uptake/conjugate bilirubin

What histologic changes occur in chronic hepatitis?

mononuclear inflammatory infiltration and hepatocyte necrosis

Why can chronic hepatitis go undiagnosed?

many chronic infections are asymptomatic and only detected by blood testing

What symptoms may occur in chronic hepatitis?

fatigue, anorexia, malaise, and RUQ pain

What severe complications can chronic hepatitis cause?

cirrhosis, variceal bleeding, encephalopathy, coagulopathy, hypersplenism, and ascites

What causes cirrhosis during chronic hepatitis?

chronic inflammation causes fibrosis and abnormal liver architecture

How does cirrhosis alter liver blood flow?

fibrosis and endothelial changes impair sinusoidal blood flow and hepatocyte access to blood

What are major consequences of portal hypertension?

ascites, varices, and splenomegaly

What complications result from liver cell failure in cirrhosis?

encephalopathy, coagulation defects, edema, bleeding tendency, and excess estrogen effects

Why are esophageal varices dangerous?

rupture can cause catastrophic bleeding and death

How do hepatitis viruses contribute to HCC?

persistent inflammation and liver regeneration increase DNA mutations and carcinogenesis

Hepatitis Virus Summary

Which hepatitis viruses are transmitted fecal-orally vs through blood?

HAV = fecal-oral; HBV/HCV = bloodborne

Which hepatitis viruses have vaccines?

HAV and HBV have vaccines; HCV does not

What are key properties of HAV?

picornavirus, ssRNA, non-enveloped, enterovirus genus

How is HAV transmitted?

fecal-oral route through contaminated food/water, poor hygiene, or unsanitary sexual activity

Why is HAV easily spread environmentally?

stable to mild heat and survives on surfaces for weeks

HAV pathogenesis

replicates in GI mucosal cells → spreads via blood → infects hepatocytes → cleared by cell-mediated immunity

Does HAV cause chronic hepatitis?

No chronic hepatitis or carrier state