Embryo/Anatomy/Physiology Flashcards
Sonic hedgehog gene (Shh)
produced at base of limbs in zone of polarizing activity
- patterning along anterior posterior axis and involved in CNS development
- mutation can cause holoprosencephaly
Wnt-7 gene
produced at apical ectodermal ridge (distal end of developing limb)
-necessary for organizing along dorsal-ventral axis
FGF gene
produced at apical ectodermal ridge (distal end of developing limb)
-stimulates mitosis of mesoderm to lengthen limbs
Achondroplasia is AD disorder of FGF-3 -> shortened limbs but normal sized head and trunk
Homeobox (Hox) genes
Segmental organization in craniocaudal direction; codes for transcription factors
Hox mutations -> appendages in wrong places (ex polysyndactyly)
When does hCG secretion begin?
implantation of blastocyst ~day 6 (detect via urine/blood 8-14 days after implantation)
What is the acrosome and flagellum of the sperm derived from?
acrosome derived from golgi apparatus
flagellum derived from centriole
When does the embryo become a bilaminar disc?
2 weeks; epiblast, hypoblast and amniotic cavity and yolk sac form
When do all 3 layers of the embryo form?
Trilaminar disc at 3 weeks
What period is most susceptible to teratogens?
weeks 3-8
What occurs at week 4 of embryogenesis?
- heart beings to beat
- upper and lower limb buds being to form
- neural tube closes
At what week does the fetus have F/M genitalia characteristics? When can it be detected by ultrasounds?
week 10, but week 16-18 by ultrasound
Embryologic derivates of surface ectoderm
- Epidermis
- Adenohypophysis (from Rathke pouch)
- Lens of eye
- Epithelial linings of oral cavity, sensory organs of ear and olfactory epithelium
- Epidermis
- Anal canal BELOW pectinate line
- Parotid, sweat and mammary glands
Embryologic derivatives of neuroectoderm
(think CNS)
- Brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland)
- Retina
- Optic nerve
- Spinal cord
Embryologic derivatives of neural crest
(think PNS and nearby non-neural structures)
- PNS (DRG, CNs, celiac ganglion, Schwann cells, ANS)
- melanocytes
- Chromaffin cells of adrenal medulla
- Parafollicular (C) cells of thyroid
- Pia and arachnoid
- Bones of skull, odontoblasts
- Aorticopulmonary septum
Embryologic derivatives of Mesoderm
- Muscle, bone, connective tissue
- Serous linings of body cavities (peritoneum),
- Spleen (from foregut mesentery)
- Cardiovascular structures
- Lymphatics
- Blood
- Wall of gut tube
- Vagina
- Kidneys
- Adrenal cortex
- Dermis
- Testes and ovaries
Embryologic derivatives of Endoderm
- Gut tube epithelium (including anal canal ABOVE pectinate line)
- most of urethra (derived from urogenital sinus)
- Luminal epithelial derivatives (lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)
Agenesis vs aplasia
Agenesis - absent organ due to absent primordial tissue
Aplasia - absent organ despite presence of primordial tissue (DiGeorge thymic aplasia)
Hypoplasia
incomplete organ development, primordial tissue present
Deformation vs disruption vs malformation
Disruption- secondary breakdown of previously normal tissue/structure
Deformation- EXTRINSIC deformation; AFTER embryonic period (weeks3-8); example compression
Malformation- INTRINSIC deformation; DURING embryonic period
Sequence error
multiple abnormalities arise from single embryologic event
Dizygotic twins
twins from 2 eggs fertilized by 2 different sperm
dichorionic and diamniotic
Monozygotic twins, cleavage at 0-4days
~25% of monozygotic twins (cleavage before implantation)
can have fused placenta or separate placenta - dichorionic and diamniotic
Monozygotic twins, cleavage 4-8days
~75% of monozygotic twins (cleavage just before implantation)
monochorionic, diamniotic
Monozygotic twins cleavage 8-12 days
Conjoined twins
Cleavage at >13 days of monozygotic twins, embryonic disc already formed at time of cleavage
monochorionic, monoamniotic
What are the fetal and maternal components of the placenta and what are their functions?
Fetal:
- cytotrophoblast (inner layer of chorionic villi)
- syncytiotrophoblast (outer layer) secretes hCG, invades uterine wall; lacks MHC I to prevent attack by maternal autoimmune system
Maternal: Decidua basalis (derived from endometrium), maternal blood in lacunae
Umbilical arteries
return deoxygenated blood from fetal internal iliac arteries to mom
Regresses into mediaL ligaments
Umbilical vein
supplies oxygenated blood from placenta to fetus, drains into IVC via liver or ductus venosus
Wharton jelly
has stem cells, fibroblasts and macrophages. surrounds vessels in umbilical cord to provide protection and support
Urachus
3rd week yolk sac forms allantois and extends into urogenital sinus
Allantois becomes urachus (duct btwn fetal bladder and yolk sac)
Regresses into mediaN ligament
Patent urachus
total failure of urachus to obliterate -> urine from umbilicus
Urachal cyst
partial failure of urachus to obliterate, fluid cavity lined with uroepithelium btwn umbilicus and bladder
Can lead to infection, adenocarcinoma
Vesicourachal diverticulum
slight failure of urachus to obliterate -> outpouching of bladder
Vitelline duct
connects yolk sac to midgut lumen and obliterates in the 7th week (omphalo-mesenteric duct)
Vitelline fistula
vitelline duct fails to close -> meconium discharge from umbilicus
Meckel diverticulum
partial closure of vitelline duct, patent portion attached to ileum (true diverticulum)
may have heterotropic gastric and/or pancreatic tissue -> melena, hematochezia, abdominal pain
1st aortic arch derivatives
part of maxillary artery (branch of external carotid)
*middle meningeal artery branches off maxillary (epidermal hematoma)
2nd aortic arch derivatives
- Stapedial artery (supplies stapedius muscle, damage causes hyperacussis)
- Hyoid artery
3rd aortic arch derivatives
Common carotid artery and proximal part of internal carotid artery
4th aortic arch derivatives
L- aortic arch
R- proximal part of R subclavian artery (note R. recurrent laryngeal nerve loops nearby)
(supplies limbs)
6th aortic arch derivatives
Proximal part of pulmonary arteries and on left ductus arteriosus (if patent ductus arteriosus machine-like murmur)
What is the pharyngeal/branchial apparatus composed of?
Branchial clefts/grooves: derived from ectoderm
Branchial arches: derived from mesoderm (muscles,arteries) and neural crest (bones, cartilage)
Branchial pouches: derived from endoderm
Branchial cleft derivatives
1st cleft -> external auditory meatus
2nd-4th clefts-> temporary cervical sinuses, which are obliterated *note: persistent cervical sinus -> branchial cleft cyst w/in lateral neck
1st branchial arch derivatives- cartilage
Meckel cartilage: Mandible, Malleus, incus, sphenoMandibular ligament
1st branchial arch derivatives- muscles
Muscles of Mastication (temporalis, Masseter, lateral and Medial pterygoids), Mylohyoid, anterior belly of digastric, tensor tympani, tensor veli palatini
1st branchial arch derivatives- nerves
CN V2 (maxillary) and V3 (mandibular)
1st branchial arch derivatives- abnormalities
Treacher collins syndrome- 1st arch neural crest fails to migrate -> mandibular hypoplasia, facial abnormalities
2nd branchial arch derivatives- cartilage
Reichert cartilage: Stapes, Styloid process, lesser horn of hyoid, Stylohyoid ligament
2nd branchial arch derivatives- muscles
Muscles of facial expression, Stapedius*, Stylohyoid, platySma, posterior belly of digastric
2nd branchial arch derivatives- nerves
CN VII (facial expression)
2nd branchial arch derivatives- abnormalities
Congenital pharyngocutaneous fistula - persistence of cleft and pouch -> fistula btwn tonsillar area and lateral neck
3rd branchial arch derivatives- cartilage, muscles, nerves
cartilage: greater horn of hyoid
muscles: Stylopharyngeus
nerve: CN IX (glossopharyngeal nerve)
4th-6th branchial arch derivatives - cartilages
thyroid, cricoid, arytenoids, corniculate, cuneiform
4th-6th branchial arch derivatives - muscles
4th arch: most pharyngeal constrictors; cricothyroid, levator veli palatini
6th arch: all intrinsic muscles of larynx EXCEPT cricothyroid
4th-6th branchial arch derivatives - nerves
4th arch: CN X (superior laryngeal branch) -> swallowing
6th arch: CN X (recurrent laryngeal branch)-> speaking
Which arches form posterior 1/3 of tongue?
arches 3 and 4
1st pouch derivatives
Middle ear cavity, eustachian tube, mastoid air cells
-contributes to endoderm-lined structures of ear
2nd pouch derivatives
Epithelial lining of palatine tonsil
3rd pouch derivatives
dorsal wings- inferior parathyroids
ventral wings- thymus
note: 3rd pouch structures end up below 4th pouch structures
4th pouch derivatives
dorsal wings- superior parathryoids
Cleft lip
failure of fusion of maxillary and medial nasal processes (formation of primary palate)
Cleft palate
failure of fusion of 2 lateral palatine processes OR failure of fusion of lateral palatine processes with nasal septum and/or median palatine process (formation of secondary palate)
Paramesonephric (Mullerian) duct
Default, develops into F internal structures
- fallopian tubes
- uterus
- upper 2/3 of vagina (lower 1/3 derived from urogenital sinus)
Mullerian agenesis
primary amenorrhea due to lack of uterine development in females w fully developed secondary sexual characteristics (functional ovaries)
Mesonephric (Wolffian) duct
Develops into internal male structures (except prostate)
-seminal vesicles, epididymis, ejaculatory duct, ductus deferens
Female - remnant becomes Gartner duct
SRY gene
SRY on Y chromosome -> testis-determining factor -> testes development
- > sertoli cells -> Mullerian inhibitory factor-> degeneration of Mullerian duct (female internal genitalia)
- > Leydig cells -> testosterone -> stimulates Wolffian duct -> male internal genitalia (minus prostate)
Septate uterus
incomplete resorption of septum, decreased fertility
Bicornuate uterus
Incomplete fusion of Mullerian ducts -> increases risk of pregnancy complications
Uterus didelphys
Complete failure of Mullerian ducts to fuse -> 2 uteruses, vaginas and cervixes
pregnancy possible
What are the M/F homologs that are derived from the genital tubercle?
M (DHT)/F (Estrogen)
Glans penis/ Glans clitoris
Corpus cavernosum and spongiosum/ vestibular bulbs
What are the M/F homologs that are derived from the urogenital sinus?
M (DHT)/F (Estrogen)
Bulbourethral glans (of Cowper)/Greater vestibular glans (of Bartholin)
Prostate gland/Urethral and paraurethral glands (of Skene)
What are the M/F homologs that are derived from the urogenital folds?
M (DHT)/F (Estrogen)
Ventral shaft of penis (penile urethra)/ labia minora
What are the M/F homologs that are derived from the labioscrotal swelling?
M (DHT)/F (Estrogen)
Scrotum/ Labia majora
What are the male and female remnants of the gubernaculum (band of fibrous tissue)
male: anchors testes w/in scrotum
female: ovarian ligament+ round ligament of uterus
What are the male and female remnants of the processus vaginalis (evagination of peritoneum)
Male: tunica vaginalis (if patent can cause hydrocele)
Female: obliterated
Ovarian/Testicular venous drainage
L ovary/testes -> L ovarian/testicular vein -> L renal vein -> IVC
R ovary/testes -> R ovarian/testicular vein - IVC
Gonadal lymphatic drainage
Ovaries/testes -> para-aortic (retroperitoneal) LNs
Distal vagina/vulva/scrotum -> superficial inguinal nodes
Proximal 2/3 of vagina/uterus -> obturator, extermal iliac and hypogastric nodes
Infundibulopelvic ligament (suspensory ligament of the ovary)- what does it connect and what structures does it contain?
Connects ovaries to lateral pelvic wall
Structures contained: ovarian vessels (come from abdominal aorta)
Cardinal ligament- what does it connect and what structures does it contain?
Connects cervix to side wall of pelvis
Structures contained: uterine vessels (from internal iliac vessels)
note risk of injuring ureter during ligation of uterine vessels in hysterectomy since ureter passes under
Round ligament of the uterus- what does it connect and what structures does it contain?
Connects uterine fundus to labia majora
Structures contained: none
Derivative of gubernaculum, travels through round inguinal canal; above artery of Sampson (anastamosis of uterine and ovarian artery)
Broad ligament- what does it connect and what structures does it contain?
Connects uterus, fallopian tubes, and ovaries to pelvic side wall
Structures contained: ovaries, fallopian tubes, round ligaments of uterus
Comprised of mesosalpinx, mesometrium and mesovarium
Ovarian ligament- what does it connect and what structures does it contain?
Connects medial pole of ovary to lateral uterus
Structures contained: none
Derived from gubernaculum
How does the uterus epithelium change from the follicular phase to the luteal phase?
follicular phase: columnar epithelium with long tubular glands
luteal phase: columnar epithelium with coiled glands
What type of epithelium lines the vagina, ectocervix, transformation zone, endocervix, uterus, fallopian tube, and ovarian outer surface
Vagina and ectocervix: nonkeratinized stratified squamous epithelium
Transformation zone: squamocolumnar junction
Endocervix and uterus: simple columnar epithelium
Fallopian tube: simple columnar epithelium, ciliated
Ovary (outer surface): simple cuboidal epithelium
When does the uterus elevate during the female sexual response?
excitement phase
What is the pathway of sperm during ejaculation?
Seminiferous tubules Epididymis Vas deferens Ejaculation duct Urethra Penis
Where does maturation of sperm occur?
Majority of maturation takes place in epididymis, final maturation takes place in vagina
What is the autonomic innervation of erection, emission, ejaculation?
Erection: Parasympathetic NS (pelvic nerve)
-> NO increases cGMP (+ with PDE5 inhibitors like sildenafil) -> smooth muscle relaxation -> vasodilation of corpus spongiosum
(NE->increase intracellular Ca2+ -> vasoconstriction -> antierectile)
Emission- Sympathetic NS (hypogastric nerve)
-> just before ejaculation; sperm released from epididymis
Ejaculation- visceral and somatic nerves (pudendal nerve)
Spermatogonia (germ cells)
maintain germ pool and produce primary spermatocytes -> secondary spermatocytes -> spermatids -> spermatozoon
Sertoli cells (non-germ cells)
Line seminiferous tubules
- secrete inhibin -> inhibits FSH
- Secretes androgen binding protein -> maintain LOCAL levels of testosterone
- Tight jxn btwn cells creates blood-testes barrier -> isolates gametes from immune system
- support spermatozoa
- regulate spermatogenesis
- produce MIF
- Temperature sensitive: less sperm and inhibin production with increased temps (varicocele, cryptorchidism)
Converts testosterone and androstenedione to estrogen via aromatase
(homolog of female granulosa cells)
Leydig cells
Located in interstitium
secretes testosterone in presence of LH, unaffected by temperature
(homolog of female theca cells)
What are sources of estrogen?
Ovary (17beta-estradiol) Placenta (estriol) Adipose tissue (estrone via aromatization)
What are the functions of estrogen?
- Development of female genitalia and breast, fat distribution
- Growth of follicle, endometrial proliferation, increases myometrial excitability
- upregulates estrogen, LH and progesterone receptors
- feedback inhibition of FSH and LH
- LH surge
- stimulates prolactin secretion
- increase transport proteins, sex-hormone binding globulin (SHBG)
- increases HDL and decreases LDL *cardio protective
- closing of epiphyseal plates
How does estrogen change in pregnancy?
50x increase in estradiol and estrone
1000x increase in estriol
How does pulsatility of GnRH affect LH and FSH release?
low amplitude, high frequency -> stimulates FSH
high amplitude, low frequency -> stimulates LH
What enzymes in which cells convert cholesterol to androgens to estrogens?
LH stimulates desmolase in theca interna cell to convert cholesterol to androgens
The androgens are transported to granulosa cell where stimulation by FSH causes aromatase to convert androgens to estrone, 17beta hydroxylase converts estrone to estradiol
Where are estrogen receptors located?
cytosol, translocate to nucleus when bound by estrogen
Where is progesterone produced?
corpus luteum (up to pregnenalone -> progesterone) testes
What are the functions of progesterone?
- stimulation of endometrial glandular secretions and spiral artery development
- maintenance of pregnancy
- decreases myometrial excitability
- produces thick cervical mucus to prevent sperm entry
- increases body temp
- inhibits gonadotropins (LH, FSH)
- uterine smooth muscle relaxation (prevents contractions)
- decreases estrogen receptor expression
- Fall in progesterone after delivery disinhibits prolactin
- high progesterone = ovulation
Tanner stages of sexual development
I - prepubertal (halted here in Turner syndrome)
II - public hair appears (pubarche); breast buds form (thelarche)
III - public hair darkens and becomes curly; penis length increases; breasts enlarge
IV - penis width increases, darker scrotum, development of glans; raised areolae
V - Adult; areolae no longer raised, hair on thighs
How long are the follicular (proliferative) and luteal (secretory) phases?
follicular - varies
luteal - always 14 days
ovulation day + 14days=menstruation
MuCune Albright syndrome
GNAS1 mutation -> increases FSH receptor function; precocious puberty
At what stage are primary oocytes arrested?
Arrested in prophase I until ovulation (diploid)
At what stage are secondary oocytes arrested?
Arrested in metaphase II until fertilization (haploid)
Ovulation
increased estrogen increases GnRH receptors on anterior pituitary -> estrogen surge stimulates LH release -> ovulation (rupture of Graafan follicle)
Temperature incerases
Mittelschmerz
mid-cycle ovulatory pain, can mimic appendicitis
Lactation
post delivery-> decrease in progesterone and estrogen disinhibits lactation
Suckling -> increases nerve stimulation -> increased oxytocin and prolactin
prolactin-lactation, decreases repro fxn
oxytocin-milk let down, promotes uterine contractions
What does breast milk contain?
Passive immunity source:
maternal immunoglobulins, mostly IgA
macrophages
lymphocytes
Associated with decreased risk for child to get asthma, allergies, DM and obesity; decreased risk for mother to get breast and ovarian cancer
*requires vitamind D supplementation
What is the source of hCG? What are its functions and when is it typically high and low?
source: syncytiotrophoblast of placenta
Function: maintain corpus luteum (progesterone) by acting like LH for first 8-10weeks, after that placenta synthesizes own estriol and progesterone
- identical alpha subunit as Lh, FSH, TSH
- higher hCG in multiple gestations, hydatidiform moles, choriocarcinomas, Down syndrome
- lower hCG in ectopic/failing pregnancy, Edward and Patau syndromes
What causes menopause?
low estrogen due to decline in number of ovarian follicles
avg age of onset is 51yrs (earlier in smokers)
*if before 40yo, can indicate premature ovarian failure
-usually preceded by several years of abnormal menstrual cycles
Hormonal changes: low estrogen, much higher FSH, high LH, high GnRH
*very high FSH is specific for menopause (loss of negative feedback from less estrogen)
What are symptoms of menopause?
Hot flashes Hirsutism Atrophy of vagina Osteoporosis Coronary artery disease Sleep distrubances
Spermiogenesis versus spermatogenesis
spermATOgenesis: begins at puberty, spermatogonia -> spermatids full development takes 2 months; occurs in seminiferous tubules
spermIOgenesis: spermatids mature into spermatozoon; loss of cytoplasmic contents, gain of acrosomal cap; occurs mostly in epididymis
Where are the androgens produced and what is their relative potency?
DHT>testosterone> androstenedione
Testis: DHT and testosterone
Adrenal cortex: Androstenedione
What are the functions of testosterone?
- differentiation of internal genitalia (except prostate)
- growth spurt: penis, seminal vesicles, sperm, muscle, RBCs
- deepening of voice
- closing of epiphyseal plates (via estrogen)
- libido
What are the functions of DHT?
Early: differentiation of penis, scrotum, prostate
Late: prostate growth, balding, sebaceous gland activity
In males how are androgens converted to estrogen?
by cytochrome P450 aromatase (in adipose and testis)
What hormones are responsible for BPH?
DHT and estrogen (increased estrogen ratio causes increased DHT density on prostate)
