Medical Physiology Block 7 Week 4 Flashcards
Describe mitosis.
cell division in somatic cells
five phases: prophase, metaphase, anaphase, and telophase
Sister chromatids (two copies of the same DNA on a chromosome) of each chromosome split, one going to each daughter cell during anaphase of the single mitotic division
Describe meiosis.
N= 23; begins with duplication of DNA, like mitosis (4N)
round 1: homologous chromosomes separate during meiosis I (2N); crossing over prophase I
round 2: sister chromatids separate (1N); like mitosis
One spermatogonium yields how many spermatids? One oogonium yields how many oocytes?
four; one mature oocyte and two polar bodies
What is the chromosome number of a zygote?
2N
Describe the Y chromosome.
small and acrocentric; when a Y chromosome is present, the individual develops as a male
How many pairs of chromosomes are the same size in the female karyotype?
8
Describe differentiation of the indifferent gonad in women. men?
In embryos with an XX sex chromosome complement, the cortex develops into an ovary, and the medulla regresses
In embryos with an XY sex chromosome complex, the medulla differentiates into a testis, and the cortex regresses
Are two X chromosome necessary for normal ovarian development?
Yes
What is the testis-determining gene?
SRY on Y chromosome (short arm)
How can sexual differentiation differ from the expected results driven by the genotype?
If the gonads fail to produce the proper messengers, if other organs (the adrenal glands) produce abnormal levels of sex steroids, or if the mother is exposed to chemical agents (synthetic progestins and testosterone) during pregnancy, sexual development of the fetus may deviate from that programmed by the genotype
Describe migration of primordial germ cells. What is the composition of the gonad?
migrate along the mesentery of the gut (originate from the endodermal epithelium of the yolk sac); Migration of primordial germ cells (controlled by chemokine (CXC motif) receptor and CXCR4 and the chemoattractants stromal-derived factor 1; integrins and RTKs are required (coactivators?))
eventually take up their position embedded in gonadal ridges
The gonad forms from a portion of the coelomic epithelium, the underlying mesenchyme, and the primordial germ cells that migrate from the yolk sac.
What is the rete testis?
The rete testis is a system of thin, interconnected tubules that develop in the dorsal part of the gonad (drain the seminiferous tubules)
What hormones regulate the development of male internal genitalia? external genitalia?
androgens (testosterone) produced by the developing testis cause development of the wolffian duct and degeneration of the Mullerian ducts (AMH)
testosterone and DHT cause masculinization of the external genitalia
What hormones regulate development of the female internal genitalia? external genitalia?
In the female embryo, the mullerian ducts develop, whereas the wolffian ducts degenerate; in the absence of a functioning testis, the left and right mullerian ducts develop as the fallopian tubes (oviducts), the uterus, and the upper third of the vagina (internal genitalia)
Absence of androgens causes the external genitalia development to be female
Describe the mesonephros.
Mesonephros has glomeruli and renal tubules which empty into the mesonephric duct, which, in turn, carries fluid to the urogenital sinus (developing bladder)
What structures develop from the wolffian ducts?
vas deferens, seminal vesicles, and ejaculatory duct (and prostate gland?)
Describe Mullerian ducts.
The paramesonephric or mullerian ducts develop as invagination of the coelomic epithelieum on the lateral aspects of the mesonephros; run cadually and parallel to the mesonephric ducts
In the caudal region, mullerian ducts cross ventral to the mesonephric ducts and fuse to form a cylindrical structure, the uterovaginal canal
Does a mature mesonephros exist in men? women?
Yes; proximal end of the epididymis
No
Does development of Mullerian ducts require the ovaries?
No
What is the result of castration on development of wolffian ducts?
development of Mullerian duct instead (no testosterone or AMH)
external genitalia proceed normally
Describe antimullerian hormone.
member of inhibins and activins family (glycosylated, disulfide-linked subunits; activity in c-domain)
transcription may be initiated by SRY
What is the cloaca? What happens to it during development?
A tubular structure called the cloaca is the common termination of the urogenital and gastrointestinal systems (membrane separates the tube from the amniotic fluid)
Wedge of mesenchymal tissues separates the cloaca into a dorsal and ventral cavity (dorsal cavity is the rectum and the ventral cavity of the urogenital sinus)
Both the wolffian and müllerian ducts empty into the urogenital sinus
How many regions are there in the urogenital sinus?
three
In males, the vesicle becomes the urinary bladder, the pelvic part becomes the prostatic part of the urethra, and the phallic part becomes the initial portion of the penile urethra (remnants of the vagina sometimes persist as a prostatic utricle)
In the female, the vesicle part also develops into the urinary bladder, the pelvic part becomes the entire female urethra, and the phallic portion develops into the vestibule of the vagina (urethra, vagina, and the ducts of the greater vestibular gland of Bartholin empty into this vestibule)
Why does the female have separate openings for the urinary and reproductive systems?
A solid core of tissue called the vaginal plate grows caudally from the posterior wall of the urogenital sinus. The lumen of the vagina forms as the center of this plate resorbs. Thus, the female has separate openings for the urinary and reproductive systems.
During early fetal development, the hymen (a think membrane) separates the lumen of the vagina from the cavity of the urogenital sinus
Describe development of the genital tubercle in both men and women.
The genital tubercle develops on the ventral side of the cloacal membrane; as a result of elongation of the genital tubercle, a phallus develops in both sexes
glans penis in men and clitoris in women
Describe differences in the urogenital folds between men and women.
The paired urogenital folds give rise to the ventral aspect of the penis in the male and the labia minora in the female
fuse in males pushing urethral orifice to the tip of the penis and remain separate in women
Describe differences in the urethral grooves of men and women.
After formation of the urogenital opening, the urethral groove forms on the ventral side of the phallus (continuous with the opening); the bilateral urogenital folds fuse over the urethral groove to from an enclosed spongy urethra
Describe differences in the genital or labioscrotal swellings in males and females.
In the male, the genital or labioscrotal swellings fuse to give rise to the scrotum; in females, however, the labioscrotal swellings fuse anteriorly to give rise to the mons pubis and posteriorly to form the posterior labial commissure (the unfused labioscrotal swellings give rise to the labia majora)
What causes the early increase in the number of Leydig cells and secretion of testosterone in gestational men?
maternal hCG or fetal luteinzing hormone
How do sex steroids act on the brain?
aromatase
Describe pulsatile secretion of GnRH in males and females.
men- tonic; women- cyclic
In women, progesterone is responsible for development of what structures? estrogen? what other hormones contribute to breast development?
Progesterone is primarily responsible for the development of the alveoli; estrogen is the primary stimulus for development of the duct system that connects the alveoli to the exterior
Insulin, growth hormone, glucocorticoids, and thyroxine contribute to breast development
T/F: The male gamete makes a considerable contribution to the cytoplasm of the zygote?
F
T/F: Are germ cells totipotent?
T; “ultimate stem cells”
Describe germ cell division in C. elegans.
Asymmetric cell division (one daughter cell loses totipotency (somatic) and the other daughter cell retains totipotency (germline))
The different fates of the germline and somatic cells are controlled by certain proteins that are retained in the germline but destroyed (by ubiquination) in the somatic cells
What are pathologies of germ cells?
infertility and cancer
Describe germ cell colonization of the gonads.
cells stop moving and enter proliferative state; germ cells in females enter meiosis and arrest in prophase I (germ cells in males arrest in mitosis until puberty);
arrange into sex cords to induce gonadogenesis (Stimulate cells of the adjacent coelomic epithelium and mesonephros to proliferate and form compact strands of tissue called primitive sex cords (swelling medial to each mesonephros))
What is the importance of sex cords and mature gonads?
Appears to be a protective barrier and a niche for development of gametes (from germ cells)
Describe transcription factor regulation of male gonadal differentiation. female gonadal differentiation?
Male transcription factors (Sertoli cell development) : SRY, Sox9, FGF9 (inhibits WNT4), PTGDS
Female transcription factors (Granulosa cell development) : WNT4, RSPO1, beta-catenin (inhibits Sox9), FOXL2 (inhibits Sox9), and ESR1&2
Are Sertoli and granulosa cells terminally differentiated?
evidence suggest they are not
What structures transport the egg and sperm within the female genital tract?
cilia and smooth muscle
Describe capacitation of the spermatozoa.
occurs in the female genital tract enhances the ability of the sperm cell to fertilize the ovum (the removal or modification of a protective protein coat from the sperm cell membrane)
Where does sperm come in contact with the oocyte?
ampullary portion of the fallopian tube
Describe steps in fertilization.
S1: The sperm cell weaves past follicular cells and binds to the zona pellucida (on ZP3 receptors)
S2: A rise in intracellular calcium in the sperm cell triggers the exocytosis of the acrosome, which contains hydrolytic enzymes
S3: Hydrolytic enzymes contained in the acrosomal cap are release and dissolve the zona pellucida; the whip-like action of the tail pushes the sperm head toward the oocyte membrane
S4: With the head of the sperm now lying sideways, microvilli on the oocyte surround the sperm head (two membrane fuse); contents of sperm cell enter the oocyte (similar concept to viral entry?; only the cytoplasmic portions of the head and tail enter the oocyte)
S5: A rise in intracellular calcium in the oocyte triggers the cortical reaction, in which there is exocytosis of granules that previously lay immediately beneath the plasma membrane; the enzymes released leads to changes in zona pellucida proteins, causing the zona pellucida to harden (preventing the entry of other sperm cells)
S5/2: The rise in intracellular calcium in the oocyte induces the completion of the oocyte’s second meiotic division, and the formation of the second polar body, which usually lies next to the first polar body
S6: The head of the sperm enlarges (chromosomes decondense) to become the male pronucleus (cytoplasmic portion of the sperm’s tail degenerates)
S7: the male and female pronuclei fuse
What is the morula stage and what part of the female genital tract does it develop in?
The ovum is fertilized in the ampullary portion of the fallopian tube several hours after ovulation and the conceptus remains in the fallopian tube for about 72 hours, during which time it develops to the morula state (solid mass of 12 or more cells), receiving nourishment from fallopian tube secretions
When does morula develop into blastocyst?
After the morula rapidly moves through the isthmus of the uterine cavity, it floats freely in the lumen of the uterus and transforms into a blastocyst (ball-like structure with a fluid-filled inner cavity)
Describe the composition of the blastocyst. Does it attach to the endometrium immediately?
Surrounding the blastocyst cavity is a thin layer of trophoectoderm cells that form the trophoblast (develops into the amnion, yolk sac, and fetal portion of the placenta)
On one side of the cavity, attached to the trophoblast, is an inner cell mass, which develops into the embryo proper
The blastocyst floats freely in the uterine cavity for about 72 hours before it attaches to the endometrium
Why is there a delay between the entry of the blastocyst into the uterine cavity and its implantation?
The embryo must be prepared to draw nutrients from the endometrium on arrival in the uterine cavity, and the endometrium must be prepared to sustain the implantation of the blastocyst
Describe decidualization.
maintenance of precidualization which is characterized by stroma transforming into decidual cells that spread across the superficial layer of the endometrium to give rise to the zona compacta and to separate it from the deeper, glandular zona spongiosa
What substances are secreted and/or produced by the endometrium? What hormone promotes these secretions? What is the function of pinopods?
The endometrium secretes cholesterol, steroid, iron and fat-soluble vitamins; also synthesizes matrix substances, adhesion molecules, and surface receptors for matrix proteins
Progesterone-dependent
Pinopods endocytose macromolecules and uterine fluid and absorb most of the fluid in the lumen of the uterus during the early stages of embryo implantation (more intimate environment for uterus and embryo)
When do pinopods appear in reference to the menstrual cycle?
between day 19 and 21
What does the blastocyst secrete to facilitate implantation?
Blastocyst releases immunosuppressive agents to avoid rejection by the maternal cellular immune system
hCG secreted by trophoblast of the early blastocyst (promotes trophoblast growth and placental development; has protease activity and may have a role in adhesion)
What is one important event that happens prior to the initiation of implantation?
zona pellucida that surrounds the blastocyst degenerates (hatching)
may be accomplished by plasmin
Describe the three stages of implantation.
Apposition occurs in an endometrial crypt and occurs at a site where the zona pellucida is ruptured or lysed
The trophoblast appears to attach to the uterine epithelium through the microvilli of the trophoblast (integrins, fibronectin, heparin and heparan sulfate proteoglycans, adhesion of the trophoblast may dislodge the uterine epithelial cells from their basal lamina and may therefore facilitate access of the trophoblast to the basal lamina for penetration)
As the blastocyst attaches to the endometrial epithelium, the trophoblastic cells rapidly proliferate, and the trophoblast differentiates into an inner cytotrophoblast and an outer syncytiotrophoblast (By degrading the ECM, MMPs and serine proteases may control both the proliferation and invasion of the trophoblast into the endometrium; Decidual cells degenerate in the region of the invading syncytiotrophoblast and thus provide nutrients to the developing embryo; As the finger-like projections of the syncytiotrophoblast invade the endometrium, they reach the maternal blood supply and represent a primordial form of the chorionic villus of the mature placenta)
Describe the primary chorionic villi.
Within 12 to 15 days after fertilization, some cytotrophoblasts proliferate and invade the snycytiotrophoblast, to form finger-like projections that are the primary chorionic villi.
Describe the secondary chorionic villi.
With further development, mesenchymal cells from the extraembryoic mesoderm invade the primary chorionic villi (secondary chorionic villi)
will form fetal blood vessels de novo
Describe the microvascular network of the mature placenta.
spiral arteries from the mother empty directly into the intervillous space (functional capillary bed), which is drained by maternal veins
What regulates the flow of maternal blood in the intervillous space?
The principal factors that regulate the flow of maternal blood in the intervillous space are maternal arterial pressure, intra-uterine pressure, and the pattern of uterine contraction (attenuate arterial inflow and disrupt venous drainage)
How does blood exit the fetus into the placenta and the mother?
umbilical arteries branch repeatedly beneath the amnion, penetrate the chorionic plate, and then branch again within the chorionic villi
What generates the intervillous space?
Lacunae are fluid-filled holes in the invading syncytiotrophoblast (The lacunae, filled with maternal blood, eventually merge with one another, to create one massive, intercommunicating intervillous space)
What is the function of the amniotic fluid?
mechanical buffer and thus protects fetus from external, physical insults and serves as a mechanism by which the fetus excretes many waste products
Does the fetus have a higher or lower affinity for carbon dioxide compared to an adult?
lower
What is the energy source used by the fetus? How does it obtain macromolecules?
fatty acids and ketones (stored as fuel in preparation for the early neonatal period)
Placenta stores vast amounts of proteins, polypeptides, glycogen, and iron (reservoir)
What is the effect of progesterone on uterine motility and contractions?
reduces and inhibits, respectively
Describe the maternal-placental-fetal unit.
Mother supplies most of the cholesterol as LDL; placenta can generate progesterone and transfer it back to the mother
Fetus produces DHEA and its derivatives (cannot make progesterone or any of the key estrogens); placenta is a massive sink for the weak androgens preventing the masculinization of female fetuses
Fetus conjugates steroid derivative to sulfate, reducing their biological activity (transferred to placenta which removes the sulfate group and transfer the weak androgens to the mother)
What is the mean duration of pregnancy?
40 weeks since the last menses
Describe increases in the mother’s blood volume during pregnancy.
The maternal blood volume starts to increase during the first trimester, expands rapidly during the second trimester, and finally achieves a plateau during the last several weeks of pregnancy (rise in plasma volume is earlier and ultimately greater than increase in RBCs)
Elevated progesterone and estrogens cause vasodilation that decreases peripheral vascular resistance and thus renal perfusion (RAAS)
Increase in blood volume protects mother and fetus against the deleterious effects of impaired venous return in the supine and erect positions
What happens to AVP release during pregnancy?
Pregnancy causes a leftward shift of the relationship between AVP release and plasma osmolality
Does cardiac output increase in the mother during pregnancy?
Yes; primarily in third trimester (increase in stroke volume and some increase in heart rate)
How does the distribution of blood flow change in pregnancy?
Increased renal, uterine, heart, skin, and breasts blood flow (no changes to flow to the brain, gut, and skeleton)
Does MAP increase during pregnancy?
No; slight increase in the third trimester compared to rest of pregnancy (still remains at or below normal)
What position generates a hypotensive state in late pregnancy?
In the supine position in late pregnancy, the fundus of the enlarged uterus rests on the inferior vena cava, thereby impeding venous return to the heart.
What happens to breathing in pregnant women?
The level of the diaphragm rises, probably reflecting the relaxing effects of progesterone on the muscle (net decrease in RV and FRC; pulmonary resistance falls facilitating airflow; less effective forced expiration)
Pregnancy increases tidal volume and thereby increases alveolar ventilation (mild respiratory alkalosis compensated by secreting some bicarbonate in the kidney)
What are recommended supplements for pregnant women?
Recommended supplementation of elemental iron is 60 mg/day, taken in the form of a simple ferrous iron salt
The weight gain during pregnancy is a result of what physiological change?
The interstitial fluid expansion may be partly the result of increased venous pressure created by the large pregnant uterus and partly caused by aldosterone-dependent sodium retention
Is failure to gain weight an ominous sign?
Yes; Birth weight parallels maternal weight, and neonatal mortality rises with low birth weight
Is the uterus primarily quiescent during pregnancy?
Yes; Throughout most of pregnancy, the uterus is quiescent (promoted by progesterone and relaxin)
Describe the role of prostaglandins in pregnancy.
The uterus, the placenta, and the fetal membrane synthesize and release prostaglandins (F2 and E2)
paracrine signaling onto uterine smooth muscles (stimulate contraction, potentiate contractions induced by oxytocin by promoting gap junction formation, and are important for softening, dilating, and thinning the cervix accompanied by invasion of tissue by neutrophils
What over-the-counter medication can inhibit labor?
aspirin
Do prostaglandin levels decrease just before and during labor?
No; increase
Describe oxytocin signaling.
Circulating oxytocin binds to g alpha protein coupled receptors on the plasma membrane of uterine smooth muscle cells
stimulates myosin light chain kinases; also binds to receptor on decidual cells stimulating prostaglandin production
What stimuli increase prostaglandin production? oxytocin secretion?
uterine contractions and oxytocin; stretching of the uterus (estrogen increases the number of receptors)
Describe the organization of the mammary gland.
alveolus surrounded by contractile myoepithelial cells and adipose tissue
Organized into lobules, each of which drains into a ductule (drains into a duct)
Ampulla is a small reservoir and the lactiferous duct carries secretions to the outside
What are the components of maternal milk?
Milk is an emulsion of fats in an aqueous solution containing lactose, lactalbumin and casein, potassium, calcium, sodium, chloride, and phosphate.
Can newborns tolerate concentrated cow’s milk?
No
How is milk produced?
proteins lactalbumin and casein are synthesized in the ER and sorted in the Golgi; alveolar cells add CaPO4 to the lumen of the secretory vesicle; lactose synthetase in the lumen of the Golgi catalyzes synthesis of lactose; water enters the vesicle by osmotic gradient generated by lactose;
the basolateral membrane of the alveolar cells takes up maternal immunoglobulins by receptor-mediated endocytosis
exocytosis discharges the contents of the vesicle into the lumen of the alveolus (lipids are secreted into the lumen in a membrane-bound sac)
Describe regulation of prolactin secretion.
Dopamine (PRL-inhibitor factor) inhibits the release of prolactin from lactotrophs
The removal of inhibition promotes PRL release (requires decrease in estrogen and progesterone)
Suckling is the most powerful physiological stimulus (afferent neural pathway)
What are secretagogues of prolactin? What alters the sensitivty of lactotrophs?
PRL-releasing factors: TRH, angiotensin II, substance P, beta endorphin, and AVP
Estradiol increases the sensitivity of the lactotroph to stimulation by TRH; decreases the sensitivity of the lactotroph to inhibition by dopamine
What are the actions of prolactin on the breast?
promotion of mammary growth (mammogenic), the initiation of milk secretion (lactogenic), and the maintenance of milk production once it has been established (galactopoietic effect)
Describe prolactin signaling pathway.
binds to tyrosine kinase-associated receptor (present in breast, ovary, and liver)
Stimulates transcription of lactalbumin and casein
Does prolactin secretion remain high in a breast-feeding women?
Yes; as long as suckling continues
What is the effect of oxytocin on the breast?
Oxytocin enhances milk ejection by stimulating the contraction of the network of myoepithelial cells surrounding the alveoli and ducts of the breast (galactokinetic effect); release of pre-existing milk: “let-down”
neurogenic reflex as a result of suckling
What stimuli increase oxytocin release? which suppress?
the site or sound of an infant or suckling behavior; suppressed when fear, anger, and other stresses are encountered
What hormones does the behavior of neonatal suckling inhibit?
Suckling likely reduces the release of gonadotropin-releasing hormone by neurons in the arcuate nucleus and the preoptic area of the hypothalamus
delays ovulation and normal menstrual cycles
Describe maturation of spermatids to spermatozoa (spermiogenesis).
loss of most of the cytosol and production of cilia for motility; compaction of the nucleus
Sperm are nestled between two Sertoli cells; the head is embedded in the Sertoli cell and the tail is in the lumen of the seminiferous tubule; individual spermatids may be linked to one another (gap junctions?)
Describe spermiation.
Spermiation is process by which the heads of the spermatozoa are released from the Sertoli cell
Are developing sperm in contact with the circulation?
No: The developing sperm are not in contact with the circulation and rely on the Sertoli cells for their supply of nutrients and elimination of metabolic waste.
Where is mature sperm stored?
sperm are stored in the lower part of the epididymis, a special coiled duct connected to the vas deferens
What is the final step in sperm maturation?
The final step in sperm maturation is capacitation which consists primarily of changes in the acrosome that prepare it to release enzymes needed to penetrate the zona pellucida (takes place in the female genital tract)
What is a complication of in vitro fertilization treatment?
increased incidence of aneuploidy and nondisjunction
What cells in the male gonad are granulosa cells analagous to?
Sertoli
Does the first polar body divide?
Yes; the final egg has three polar bodies
How does receptor composition change near the end of the follicular phase of the ovarian cycle? What happens with further gonadotropin stimulation? What happens if the gonadotropins are directed to a more dominant follicle?
Towards the end of the follicular phase, some cells of the granulosa layer develop receptors for estrogen and FSH and the theca cells develop receptors for LH
If FSH and LH are present then the follicles will continue to develop
If not stimulated by gonadotropins, the follicle dies (atresia)
What hormone released during the ovarian cycle is referred to as “pro-gestation”?
progestins (progesterone)
Which structure in the female gonad is anatomically termed the yellow body?
corpus luteum
Describe the trajectory of fetal growth in each trimester.
The growth trajectory of fetal mass is relatively flat during the first trimester, increases linearly at the beginning of the second trimester, and rises rapidly during the third trimester
Does the placenta grow by both hyperplasia and hypertrophy? fetus?
Yes
growth of the fetus occurs almost entirely by hyperplasia; thus, DNA content increases linearly in all fetal organs beginning early in the second trimester.
What factors determine growth during the first half of gestation? second half?
genetics;
placenta, hormones, environment, and metabolites
T/F: Fetal growth closely correlates with placental weight?
T
Describe metabolism in the fetus.
the fetus normally has little need for gluconeogenesis, and the levels of gluconeogenic enzymes in the fetal liver are low.
Glucocorticoids in the fetus promote the storage of glucose as glycogen in the fetal liver, a process that increases greatly during the final month of gestation in preparation for the increased glycolytic activity required during and immediately after delivery (fetal glucose metabolism becomes sensitive to insulin in near term; maternal insulin cannot cross the placenta)
Before the second trimester, most of the thyroxine in the fetus is maternal; fetal production of thyrotropin and the thyroid hormone begin to increase in the second trimester, concurrent with development of the hypothalamic-pituitary portal system
What cells can produce red blood cells in the fetus? Are these cells nucleated?
he endothelium of blood vessels and the mesenchyme begin to contribute to the erythrocyte pool, shortly followed by the liver. The bone marrow, spleen, and other lymphoid tissues begin to produce red blood cells only near the end of the first trimester. All these organ systems except bone marrow gradually lose their ability to manufacture blood cells, and by the third trimester, the bone marrow becomes the dominant source of blood cells.
YES
Describe excretion pathways in the fetus.
The fetal gastrointestinal tract continuously excretes small amount of meconium into the amniotic fluid (excretory products from the GI mucosa and glands, unabsorbed residua, and engulfed amniotic fluid)
Fetus begins to urinate by the beginning of second trimester
(however, the kidney does not really begin to develop before the third trimester)
What is anabolic feature of the third trimester? What is the consequence? Do these cellular mechanisms improve with experience?
a surge in protein synthesis
increase in muscle mass
Yes: the efficiency of ribosomes at translating mRNA may improve during gestation
What else increases the fetal weight in the third trimester?
Approximately half the increase in body fat reflects increased lipid transport across the placenta, and the other half reflects increased fatty acid synthesis in the fetal liver (increased fat storage in white and brown adipose tissue)
How does the lung mature?
begins as an outpouching of the gut
During the pseudoglandular period, the lung airways resemble branching exocrine glands
The canalicular period is characterized by canalization of the airway is complete when about 17 generations of airways have formed, including the respiratory bronchioles
During the terminal sac period, the respiratory epithelium thins greatly, and the capillaries push into the alveolar sacs (surfactant synthesis in type II pneumocytes begins)
In the alveolar period, final alveolar growth occurs
What triggers production of surfactant?
Glucocorticoids (increase number of type II pneumocytes and lamellar bodies within these cells), thyroid hormones, TRH, and prolactin, as well as EGF stimulate surfactant biosynthesis
cortisol upregulates fatty acid synthase and phosphocholine transferase
What physiological mechanisms are improved in the lung by increased surfactant secretion?
lung distensibility and stability on inflation
What promotes fetal breathing?
Hypoxia and tactile stimulation of the fetus promote breathing movements (becomes more regular near term; however, breathing decreases just before labor)
What happens to the pulmonary system following labor?
The onset of labor is accompanied by increases in catecholamines and AVP, which decrease fluid production by the fetal lung and initiate its active reabsorption; the pulmonary circulation absorbs the majority of the fluid, and the pulmonary lymphatics absorb some as well
What embryonic layer is the circulatory system derived from?
mesoderm
What performs gas exchange, supplies nutrition, remove wastes, and balances both fluid and electrolytes for the fetus?
placenta
Do the inputs and output of the right and left fetal hearts mix?
Yes
Describe circulation of blood in the fetus.
Ductus venosus shunt bypasses the liver, which is largely nonfunctional; allows blood from the umbilical vein to enter the inferior vena cava directly (enters right atrium)
Foramen ovale shunts blood entering the right atrium to the left atrium (primarily flows to the head and forelimbs)
Ductus arteriosus direct blood from the pulmonary artery to the aorta
Thoracic aorta shunts blood to the placenta through paired umbilical arteries (shunts blood away from the lower trunk and abdominal viscera, including the kidneys)
Why is the ductus arteriosus patent in the fetus?
active relaxation of smooth muscle mediated by prostaglandin E2;
Why is the resistance so high in the pulmonary vasculature?
High resistance in the pulmonary vasculature is a result of hypoxic vasoconstriction and acidosis, the collapsed state of the airways, and perhaps leukotrienes
What metabolic changes accompany birth?
hypoxia, hypoglycemia, and hypothermia
What prevents blood flow from the placenta to the fetus during labor?
Stretching the umbilical arteries during delivery stimulates constriction
Sudden rise in systemic arterial oxygen partial pressure in the newborn stimulates and maintains vasoconstriction in the umbilical arteries
T/F: the first breath is normally the most difficult inspiration of a lifetime?
T: A considerable negative pressure within the intrapleural space is necessary to overcome the effects of surface tension
What stimulates breathing after delivery?
Tactile stimulation and decreased skin temperature also promote the onset of breathing
Increased sympathetic tone may stimulate breathing at the time of birth by constricting vessels to the peripheral chemoreceptors, thereby lower the local oxygen partial pressure in the microenvironment of the glomus cells and mimicking even more severe hypoxia.
What is periodic breathing? When does it happen?
consists of breaths with intermittent respiratory pauses and varying tidal volumes (REM sleep)
What happens to total peripheral resistance following the closure of the placental circulation? pulmonary resistance?
With closure of the placental circulation, total peripheral resistance doubles (aortic pressure must increase)
the increase in oxygen partial pressure and pH that occurs with breathing leads to pulmonary vasodilation (resistance decreases by more than five-fold; pressure in the upstream right ventricle falls) (prostaglandin I2 may have an effect, released by the expanded lung)
Describe blood flow to the liver following labor.
Immediately after birth, portal flow through the liver remains low
Within about three hours after term birth, constriction of the vascular smooth muscle within the ductus venosus completely occludes the shunt (Pressure in the portal vein increases markedly, thereby diverting blood in to the liver)
What causes the foramen ovale to close?
At birth, left atrial pressure beings to exceed right atrial pressure, thus causing the foramen ovale to close (reversal of pressure gradient across the atrial septum)
What happens to blood flow through the ductus arteriosus following birth?
Immediately after birth, the ductus arteriosus conducts blood from the aorta to the pulmonary artery (result of high aortic pressure and low pulmonary artery pressure)
Closes because its muscular wall constricts (lumen becomes obliterated due to thrombosis, proliferation of the vessel’s intimal layer, and growth of fibrous tissue)
circulating levels of prostaglandins drop eliminating the stimulus for vasodilation of the duct
How is the systemic vascular resistance profile of the neonate different from an adult?
Compared with the adult, the newborn has a markedly lower systemic vascular resistance and thus can achieve a relatively high blood flow with relatively low perfusion pressure
What is the neonatal period?
first four weeks of life
What is the main form of heat loss in the neonate? Why do neonates lose heat?
evaporation
large surface-to-volume ratio; limited ability to generate heat through muscle contraction; poor thermal insulation by adipose tissue
What sites in the body of a neonate contribute to nonshivering thermogenesis?
Nonshivering thermogenesis occurs in the liver, brain, and brown fat
Describe nonshivering thermogenesis
Cold stressor triggers increase in epinephrine and TSH
Epinephrine activates, particularly in brown fat, the 5’/3’-monodeiodinase responsible for the peripheral conversion of T4 to T3; also, through cAMP, activates the lipase that liberates fatty acids from triglycerides to relieve inhibition of UCP1 by ATP
T3 acts locally in brown fat to uncouple mitochondrial oxidation from phosphorylation and thereby to increase heat production (upregulation of UCP1)
Newborns have particularly high levels of brown fat in the neck and midline of the upper back
Describe metabolism following delivery.
In its first few hours, the neonate uses glycogenolysis to mobilize hepatic glycogen stores
Hypoxia, hypoglycemia, and hypothermia all stimulate the release of epinephrine from the adrenal medulla
How is the metabolic rate of a neonate compare to the metabolic rate of an adult?
Through the first year of life, the growing infant has a daily resting metabolic rate nearly double the value of a healthy young adult.
What component(s) of colostrum (milk-like substance secreted by the mammary glands) are important for neonatal survival?
IgA; factors that promote the growth of lactobacilli, which colonize the colon and may protect the infant from virulent strains of E. coli
What supplements may the infant require?
fluoride to minimize tooth decay; vitamin D is not enough sun exposure; vitamin C to prevent scurvy
Describe the fluid and acid-base imbalances that may arise in an infant.
Cannot concentrate urine as efficiently and have much greater acid load than in adult (risk for development of metabolic acidosis and dehydration)
Which immunoglobulins cannot cannot cross the placenta? Which one can?
Maternal IgA, IgE, and IgM antibodies do not generally cross the placenta in appreciable amount; IgG
Does the fetus produce its own antibodies?
Not really (isolated from antigens); may produce its own IgM
What inflammatory and immune products are produced by the fetus?
Fetuses produces complement proteins, lysozymes, and interferon gamma, which is produced by T lymphocytes and which activates B lymphocytes, macrophages, and endothelial cells
What defines a premature infant?
A premature infant is defined as open born sooner than 37 weeks after the mother’s last menstrual period (compared with the normal 40 weeks)
Premature birth generally reflects immaturity either of certain organ systems or of homeostatic mechanisms
Describe aneuploidy. (what causes it, is it more prominent in sperm or oocytes, and what are some pathologies that result from aneuploidy?)
Aneuploidy caused by defects in chromosome segregation (nondisjunction at meiosis I or II)
The vast majority of aneuploidies originate in the oocyte
Nondisjunction during cleavage results in a mosaic individuals (mitosis)
Turner syndrome (XO): germ cells cannot migrate as well from yolk sac to gonadal ridges (menopause in early 20s and streak gonads)
Klinefelter’s (XXY): males are sterile; decreased androgen production
Super female (XXX): sterile
Super male (XYY): fertile and tall (have signs of acne and aggression)
Describe Guevedoces.
Due to 5α-reductase deficiency [converts testosterone to dihydrotestosterone (DHT)].
Because DHT is absent the male external genitalia does not develop and the guavodoces males (46; XY) are born with female external genitalia.
Their testes secrete normal levels of testosterone; they have normal sex accessory ducts and glands and no mullerian ducts.
Describe blastocyst implantation and invasion.
Blastocyst attachment to the uterine wall depends upon the interaction between adhesion molecules such as selectins, integrins, and uterotrophins, expressed on both trophoblast cells and uterine epithelium
Paracrine cross-talk between embryo and uterus is needed for blastocyst implantation
Pinopods interacts with syncytiotrophoblast cells
Trophoblast cells fuse together (multinucleated)
Describe the role of the placenta during pregnancy.
The placenta produces hormones that shift the control of many regulatory functions from the mother to the fetus to insure optimal control of gestation (an example is the slight insulin resistance of the mother during pregnancy)
What is a factor that determines adult health?
prenatal health
Describe the regulation of maternal blood supply during pregnancy.
initial invasion of uterine vasculature (spiral artery) early in implantation
the only way the fetus can increase blood supply is to increase maternal blood pressure (If the trophoblast does not invade far enough into the artery, maternal hypertension may arise later in pregnancy (pre-eclampsia?))
Describe fluctuations in hCG levels during gestation.
hCG levels drop considerably following the eighth week of gestation and levels are at its lowest (plateau) by the 20th week of gestation
NOTE: Progesterone is produced by the corpus luteum for the first 2-6 weeks of gestation, when the progesterone becomes produced by the placenta through hCG
T/F: the fetal adrenal gland is larger than the kidney?
T
Describe the feto-placental unitl as described in lecture.
placenta takes cholesterol from the maternal circulation and produces pregnenolone; the placenta produces progesterone and returns it to the mother
the fetus may take up pregnenolone and produces sulfated DHEA, which the placenta uses to produce either estradiol or estriol (placenta removes the sulfate group)
Fetus has 16-hydroxylase in the liver, which is the substrate for estriol production in the placenta
What hormone only produced during gestation is a clinical parameter for the health of the fetus?
estriol
What hormone keeps the uterus quiescent during pregnancy?
progesterone
Describe the two mechanisms of human birth.
myometrium contracts and uterine cervix softens
contractions are associated with fetal hypoxia
