Repro Flashcards
Puberty
Before and after fertile years FSH > LH during fertile years LH is greater than FSH
- Increase in LH signal steroid production and onset of puberty
- In females breast buds occur before menarche
- In males growth in size of testes is driven by seminferous tubule expansion and leydig growth
- At puberty GNrH signals an increase in it’s own receptor number leading to increased pulsatile LH secretions
Sertoli Cells
- Tight junctions
- Secretions of fluid
- Nitrients (ABP)
Leydig
-Interstitial cells and secrete testosterone
Sperm
Mitotic is spermatoagonia and meotic is to spermatidis (Haploid)
Semen
- Seminal vesicles secretes: PG, fructose, citrate, and fibrinogen
- Prostate: Alkaline fluid with Zn, citrate, Ca
Capacitation
Sperm gain motility in female tract through Ca influx
-Undergo acrosome reaction which allows for acrosome to fuse with PM
Testosterone
- Leydig cells containn 17B hydroxysteroid hydrolase which converts weak androgens into testosetone
- LH increases rate of desmolase conversion
- Most stays locally to aid in spermatogenesis
- Rest goes systemic
- Testosterone is the major feedback and functioner
- Required for development of itnernal male structures
- DHT is external structures (5 alpha reductase def)
Follicular Development
- In cortex granulosa cells begin to form around follicle
- Then thecal cells begin to form outside of that and an antral follicle is formed
- Thecal cells respond to LH and secrete estrogen while granulosa cells respond to FSH and secrete aromatase
- Dominant follicle emerges and releases at ovulation. Completes first division. Arrested at metaphase 2
- Completes metaphase 2 at fertilization
Implantation
Blastocyst implants onto cell wall and requires a high progesterone concentration
-Decidua envelopes and produces synctitiotrophobasts
Estogen
- Secondary sex
- Stimlates endomertrial proliferation and contractions
Progesterone
- halts proliferation and increases maturition and secretion
- Halts contractions
Placenta
- Early pregnancy hormone levels are maintained by hCG and CL
- 2nd and thrid trimester placenta secretes pregnenalone which goes to fetal adrenals and is converted to DHEAs then diffuses back to placenta where aromatase converts to estriol
Partrution
Uterine distension causes increase in contractions
- Fetal HPA produces cortisol and increases the estrogen to progesterone ratio
- Estrogen increases prostaglandins which cause uterine contraction
- Cervical distension leads to oxytocin release
Labor
- Early part is positioning
- Second is delivery of baby
- Third is delivery of placenta.
- Oxytocin and strong contractoins prevent bleeding
Embryo
Sonic Hedgehog: AP patterning
WNT-7: Dorsal and ventral patterning
-FGF: Limb Lengthening
Hox: Segmentation and limb positioning
2 weeks
-Bilaminar
3 weeks
Trilaminar and primitive streak
3-8 weeks
-Embryonic period where organogenesis occurs. Fetus is susceptible to teratogens and neural tube defects
4 weeks
Heart
8 week
movement
10 weeks
genetalia
Endometrium
- Proliferative stage driven by estrogen and cells increase in number and size but don’t secrete
- Secretory: Progesterone. Glands become toruous and stroma becomes vacuolated with spiral arteries
Gastrulation
Epiblast (bilaminar disk) invagination and forms trilaminar disk
surface ectoderm
- Forms all external structures, skin etc
- Forms skin of oral cavity
- Forms eye and lens
- Forms AP (Craniopharyngoma)
Neuroectoderm
-CNS and neural structures. Retnia and optic nerve
Neural Crest
- PNS and autonomics
- C cells of thyrpid
- Septation of heart
- Melanocytes
- Bones of skull including odontoblasts
Mesoderm
- Muscle and connective tissue
- Spleen
- Peritoneal cavities (Spleen)
- Blood vessels and heart
- GU
- VACTERL
- Vertebral, Anal, Cardiac, TE, Renal, Limb
Endoderm
- Internal strucutures
- Gut
- Branchial Pouches (PTH and Thymus)
- Thyroid
Agnesis and Aplasia
- Agenesis is that tissue was never present
- Aplasia is that tissue was present but never grew
Sacrococygeal Teratoma
- Most common sacral mass in infants
- Remnant of caudal protion of primitive streak
Aminoglycosides
-CN 8 deafness
Tetracyclines
Teeth
Fluoroquinolones
Tendons and bones
ACEI/ARB
Renal agenesis leading to potters syndrome
Fetal Hydantoin (Carbemezepin/phenytoin)
-Microcephaly, facial anomalies, IUGR, Neural tube, cardiac, hypoplastic nails and distal digits
Lithium
-Ebstiens anomaly
Valproate
-Impairs folate metabolism leading to neural tube defects
DES
-Embyronal rhabdosarcoma
Retinol
-Cleft Palate and spontanous abortion
Warfarin
-Opthalmologic defects, bleeding, bone deformities, and aboriton. use heparin during pregnancy
FAS
-Microcephaly/holoprosencephaly, VSD and cardiac defects, mental retardation and facial defects, IUGR
Cocaine
-IUGR, premature placental rupture, baby addicted at birth
Smoking
IUGR, ADHD, preterm labor
Maternal Diabetes
Caudal regression syndrome, transposition of great vessels and neural tube defects
X rays
Retardation and microcephaly
Heroin
Tremors, irritability, yawning, rhinorrhea, etc
-Treat with opium
Twinning
- Most are dizygotic and occur from fertilization of two differnt eggs. Will always be dichorionic (Placenta) diamniotic (Amniotic sac)
- If monzygotic, split occurs of single fertilized egg early in development
- 0-4 days (25%) dichorionic and diamniotic
- 4-8 days (75%) monochorionic and diamniotic
- later is mono/mono or conjoined and is very rare
Fetal Placental Tissue
- Cytotrophoblasts are located at the inner layer and can divide
- Synctitiotrophoblasts are located at the outer layer and secrete hCG and communicate with maternal placenta
- Nutrient transfer occurs in lacunae
Umbilical Cord
2 arteires (off internal illiacs) deoxygenated blood
- 1 Vein (through DV and to heart)
- Also contains allantoic duct which communicates with yolk sac
Allantois
-Early in gestation connects yolk sac to urogenital sinus, later replaced by urachal duct
Urachal Duct
- Connects urogenital sinus to yolk sac
- Obliterated failure leads to persistance (Urine to flow through umbilicus
- Vesicourachaldiverticula which can predispose to later adenocarcinoma of bladder
Vittelline Duct
- Connects midgut to yolk sac and allows for protrusion of gut contents during embyonic period
- Normally oblierated by week7
- Remnant leads to Vitteline fistula which causes meconium leakage at birth
- Meckels diverticulum extends off terminal ileum, can have ectopic gastric glands that cause bleeding and ulceration (Periumbiliical pain)
Aortic Arches
1st: Maxillary artery becomes superficial temporal and maxillary through spinosum. Supplies nasal and deeper oral structures
2nd: Stapedial and hyoid (only ossicle not done by 1 is stapes
3rd: Common carotid and first part of internal carotid
4th: Right brachiocephalic and left goes to arch of aorta
6th: Pulmonary arteries to DA
- R recurrent laryngeal around brachiocephalic/subclavian
- L recurrent laryngeal round arch of aorta and stuck on ligamentum arteriosum
Branchial Aparatus
Arches are mesoderm
Clefts are ectoderm
Pouches are endoderm
1st Cleft
External Auditory Meatus
- rest of clefts dissapear as cervical sinus.
- Persistent cervical sinus will present as lateral neck swelling
1st Arch
- Muscle of mastication, incus, malleus, mandible
- Treacher Collins is impaired migration of the first arch
2nd arch
- Stapedial artery and stapes. muscles of facial expression
- Hyoid cartilage
3rd arch
- Glossopharyngeal and stylopharyngous muscle
- Contriubtes to posterior tongue
- Fistual leads to communication between tonsils and lateral neck
4th arch
Superior Laryngeal Nerve
- Posterior pharynx and pharyngeal constrictors
- Cricothyroid. Afferent limb of gag reflex (Elevates pharynx/palate)
- Cricoid, thyroid, coriat etc cartillages
6th arch
- Recurrent laryngeal nerve (R around subclavian) L around aorta and stuck on ligamentum arteriosum
- Muscles of larynx.
- Posterior cricoarytenoid is only one that keeps folds open
1st pouch
Endodermal strucures of ear
-Eustachian tube and middle ear, mastoid air cells
2nd pouch
-Palatine tonsils
3rd pouch
- Inferior PTH (Dorsal wings)
- Thymus (Ventral wings)
4th pouch
-Superior PTH
DiGeorge
Abnormal development of 3rd and 4th pouches. Leads to no PTH and no Thymus
MEN 2A
- RET oncogene
- Med C, Pheo, PTH
- MEN2B is mucocutaneous neuromas
Cleft Palate
Failed fushion of lateral palatine and nasal or medial palatines
CLeft lip
Failed fusion of maxillary folds with medial nasal fold
SRY
Contains TDF which is a transcription factor for MIF and testicle development
Mullerian
Internal Femal Strucutures to proximal vagina
- Deformation can lead to pirmary amenorrhea in the presence of normal hormonal status
- Bicornate uterus occurs if there is incomplete fusion of mullerian ducts leads to miscarriages and UTI
Male
Internal are encourgaed to grow by Test: Epidydymis, vas deferens, seminal vesicles ejaculatory ducts
-Scrotum, prostate and penis are encouraged to grow with DHT
Analogs
Cowpers gland-corpora
- Ventral shaft of penis is labia minora
- Scrotum is majora
Hypospadias
-improper fusion of labia minora
epispadias
- improper placement of the genitle tubercle
- Seen with bladder extrophy
Descent
Gubernaculum through internal ring (Transversalis)
- Internal oblique becomes the cremaster
- External (Superfifical ring)
- Periteoneal fold is the tunica vaginalis which is normally obliterated
Lymph Drainage
- Testis/OVaries to paraaortic
- External strucutures to superficial inguinal
- Uterus and upper vagina (Mullerian derivatives) obrotator, external illiac, hypogastric nodes
Relaxin
Released during pregnancy to allow bones and joints to loosen and accomidate pregnancy
Physiologic Changes in Pregnancy
- Increased HR and CO with decreased peripheral resistance and BP
- Increased GFR leads to physiologic glucosuria, filtered load is too high
- Elevated blood volume and decreased osmolarity, there will also be a relative dilutional anemia and increase in fibrongogen (Clotting after birth)
- Gastric emptying is slowed and respirations increase with a reduction in residual volume
Orchitis
Can produce sterilty if bilateral and will involve destruction of the parenchyma of the testes leading to decreased T and inhibin with an increase in FSH and LH
Epidydimitis
Most commonly bacterial, can be from spermatocele, but spermatocele is rarely symptomatic
-Prehns sign, where pain is reduced with testicular elevation will be present
Seminoma
Most common tumor
- Sub tunica albuginia with sheets of clear cells (Glycogen and lipids)
- Good prognosis
- Will be positive for PLAP and also hCG usually
- There is an increased risk in patients with cryptorchidism
Yolk Sac
- Grossly appears yellowish
- Microscopically will show glomeruloid schiller duval bodies and eosinophilic cells
- Elevated AFP
- Most commonly seen in young kids (5 years)
Embryonal Carcinoma
- Areas of hemorrhage and necrosis that may be painful
- Commonly a mixed tumor with large amounts of anaplastic immautre large cells
- Elevations in hCG and AFP are possible
Chorciocarcinoma
- Most common in younger patietns
- WIll have elevated hCG
- Generally a small primary with hematogenous metastasis
- Elevated hCG levels may increase androgen production and lead to gynecomastia
Teratoma
- More commonly malignant in males and the more immature the more malignant
- Mature has well formed layers of multiple tissues, commonly cartillage
- Immature is less well differentiated
Leydig
- Secrete androgens and esterogens that often leads to gynecomastia
- Reinke crystals are common
Sertoli
-Hormonally silent tumor of chrods of sertoli cells
Malignant Lymphoma
-More common testicular mass in older man. Highly malignant and poor prognosis
Prostatitis
-If chronic will induce scarring and fibroblastic proliferation
BPH
- Nodular hyperplasis in the periurethral zone
- Feels smooth on DRE
- Caused by increased androgen sensitivity of prastate and androgen levels fall
- DHT leads to increased cell survival and stromal proliferation (Hyperplasia) that leads to the urethral narrowing and clinical manifestations
- Elevatinos in free PSA
- Causes bladder hypertrophy and may cause diverticula
- Tx with alpha blockers to relax sphincter (Tamsulosin/Prazosin)
- Post Renal Azotemia which will present with initially normal values that decline and lead to azotemia
- Increased risk for ascending infection as well
Adenocarcinoma of Prostate
- Occurs in the peripheral posterior zone and is palpated as a nodular mass with obliteration of central sulcus on DRE
- Elevated levels of PSA (increased bound fraction) and PAP
- Most commonly metastasizes to bone as sclerotic lesions with increased Alk Phos
- Can metastasize to the para-aortic lymph nodes
- Tx with androgen removal )Orchiectamy) Fluatmide, leuprolide
Dysgerminoma
Most common ind turners
-PLAP sheets
Sacrococcygeal teratoma
Most common tumor of sacrococcygeal region in kids
-Teratoma that is left over from primitive streak
Choriocarcinoma
-Increase risk of Theca-Leutin cysts which occur due to increased gonadotopin secretion
Mature Dermoid
-Formed of multiple layers, often see cysts and cartillage
Immature dermoid
- More commonly seen in youger patients
- Hemorrhage and necrosis with poorly defined cells
Strumma Ovarii
-Monodermal tumor that can cause hyperthyroidism
Granulosa Cell
- Granulos cells that surroud in a follicular like pattern with eosiophilic cytoplasm
- Express aromatase and secrete excess estrogen which may be associated with endometrial hyperplasia, infertitlit, and precocious puberty
Epithelial Cell Tumors
- CA-125 is good marker for progression of disease but is not specific enough to be used as screenin
- Biggest risk factor is family history BRCA and Lynch Syndrome
- Can commonly be bilateral, especially krukenberg
Serous Adenoma
- Uniloculated cyst with fallopian tube like epithelium
- Can become large and is benign (45%)
Serous ADenocarcinoma
- Uniloculated by lined by papillary disordered grwoth strucutre may lead to hemorrhage and necrosis
- Psammoma bodies are often present
- Malignant
Mucinous
- Multiloculated that appears like GI tissue
- ADenoma is benign
- Carcinoma may cause pseudomyxoma peritonei (Along with appendiceal tumor)
Brenner Tumor
Made of transitional urothelium that has coffee bean shaped nuclei
-Benign
Kruckenberg
- Signet ring cell metastasis to ovaries from GI adeniocarcinoma
- Almost always bilateral
Fibroma
- Fibroblasts arranged in spindle shapoed parallel arrangment
- ASsociated with Pulmonary edema, Ascites
- Called Meig’s sybndrome
Fibrocystic Change
Most common in females that are premenopausal
- Blue domed cysts occur due to dilation of ducts
- Sclerosing adenosis is an increase in the number of acinini in a terminal lobule, may appear cancerous, but does not carry any risk
- Fibrosis is just hyperplasia of stroma
- Epithelial hyperplasia may occlude a duct and cause dialtion. Will always be lined by 2 epithelial layers when benign
- If there is atypia associated with epthelial hyperplasia there is an increased risk for cancer
Intraductal Papilloma
- Papillary structures with psammoma bodies extend into the duct
- There is often a double layer of epithelium and there will be perent basement membrane
- Most common cause of bleeding, and is a benign tumor
Phyllodes Tumor
Proliferation of teh stromal cells creating a large leaflike pattern
- May transfrom into malognant rarely
- Located deeper in the breast
- Surgical removal must take wide margins because of reccurenc risk
- Generally occurs late
FIbroadenoma
- Growth of stromal cells in a discrete movable hard mass
- Most commonly presents early in life and is hormone responsive
Fat Necoris
- Trauma leads to necrosis of fat and soponification by macrophages
- May show calcified image, but is completely benign
Mastitis
Most commonly caused by staph aureus and may be related to breast feeding
- Treat with antibiotics
- Be carfeul that it goes away and is not an inflammatory carcinoma
Gynecomastia
- Klienfeleters or other cause of elevated estrogen exposure
- Drugs: Spironolactone, androgens, cimetidine, digitalis, alcohol, ketocolonazole. Inhibitors of Cyps that decrease androgens and increase estrogens
Malignant Breast Cancer
- Most important risk factor is family history and associated gentic diseases. BRCA
- Other risk factors deal with increased lifetime estrogen exposure
- Associated with estrogen and progesterone receptor positivity whih is importnt for treatment
- Also EGFR ERBB2 which is blocked with traztuzumab
DCIS
Most common form of breast cancer
- Is in situ as long as basement membrane is still intact
- Can be casseous necrosis and then is called comedocarcinoma
LCIS
- Arises in both lobules and is associated with elevated estrogen exposure
- Carries an increased risk for both breasts, but in and of itself, only progresses 1/3 of the time
Invasive ductal
Most common type, invasion through basement membrane
Paget’s disease
DCIS that crawls through squamous epithelium around breast and produces erythema and pruritis
Medullary
Asscoiated with early onset and BRCA
-Fleshy and cellular with lymphocytic infiltrate. Good Prognosis
Inflammatory
Invasion of dermal lymphatics
- Poor prognosis
- Will have red and inflamed breast, differentiate from acute mastitis
Invasive lobular
Contains single file cells that must lose E cadherin to become invasive
-Commonly bilateral
