Reproductive Flashcards
(239 cards)
1
Q
Sonic Hedgehog
A
Important for early anterior posterior patterning
mutations or dysfunction may lead to holoprosencephaly
2
Q
WNT-7
A
Dorsal ventral patterning in early embryo
3
Q
FGF
A
Growth of limbs, mesodermal mitosis
4
Q
Homeobox
A
Segmentations in embryo
-Mutations leads to limb displacement
5
Q
Implantation
A
-Fertilization leading to zygote then to morula and then to blastocyst which will implant into the endometrium at day 6
6
Q
Blastocyst
A
Inner cell mass (form three layered embryo) and trophoblast layers (interact with endometrium)
7
Q
Embryonic Period
A
3-8 weeks, development of organs. Teratogens in development can occur here
8
Q
4 weeks
A
heart beats
9
Q
10 weeks
A
distinguish male and female genetalia
10
Q
Surface Ectoderm
A
- Skin
- Craniopharyngoma (oil, chol, calcifications)
11
Q
Neuroectoderm
A
CNS and glial cells
12
Q
Neural Crest
A
PNS, parafollicular C cells, pia and arachnoid, bones of skull, odontoblasts, aortopulmonary septation
13
Q
Mesoderm
A
Muscle, bone, connective tissue
- Spleen: Foregut mesoderm
- Kidney and bladder (intermediate)
14
Q
Notochord
A
Nucleus Pulposus
15
Q
Endoderm
A
- All luminal organs
- Gut, etc
- Lungs, liver, eustachian tube, PTH, thymus, thyroid follicuar cells
16
Q
Teratogens
A
- If seen before 3 weeks is often fatal
- If seen 3-8 often severe effects on organogenesis
- If seen from 8 onward defects mainly in growth and maturation
17
Q
FAS
A
Most common teratogen in US
-Microcephaly, holoprosencephaly, retardation, facial anomalies, may have cardio-respiratory anomalies
18
Q
ACEI
A
Renal anomalies, may also be CNS and Cardio. There may be less risk in first trimester and more risk in 2nd and 3rd. Mechanism involves oligohyramnios
19
Q
Alkylating Agents
A
Absence of digits and other abnormalitties
20
Q
Aminoglycosides
A
-Damage to CN 8 and impaired hearing
21
Q
Carbemazepine
A
Neural Tube, Craniofacial, Fingernail hypoplasia, IUGR
22
Q
Phenytoin
A
Microcephaly, craniofacial, hypoplastic nails, Cardiac Defects, Mental Retardation, IUGR
23
Q
Valproate
A
Interferes with folate metabolism leading to neural tube defects
24
Q
Phenobarbitol
A
Preferred drug to use for siezure disorders in pregnancy because of high protien binding.
25
Methimazole
PTU is preferred because of reduced transfer to the placenta, although evidence may be lacking
26
DES
Clear cell carcinoma of the vagina and mullerian abnormalities
27
Lithium
Ebstiens anomaly (hypoplastic R ventricle)
28
Tetracyclines
Bone discoloration
29
Warfarin
-Hydrocephalus, fetal hemorrhage, occular nerve damage (blindness), bone abnormalities, aboirtion. Heparin preferred, doesn't cross placenta because of charged nature
30
Cocaine
Crack baby will be small, addicted, and premature labor
| -Placental Abruption
31
Heroin
- Jitters, high pitched cry, fevers, diahhrea, runny nose, sneezing, vomiting, tachypnea
- Tx: methadone
32
Iodide
-Cretinism
33
Maternal Diabetes (not gestational)
- Caudal regression syndrome
- Transposition of the great vessels, PDA
- Neural Tube
34
Vitamin A
-Spontaneous abortions and cleft lip/palate
35
X Ray
Mental retardation and microcephaly
36
Dizygotic Twins
Two different fertalized eggs
| -Dichorionic diamniotic
37
Monozygotic
- Cleave bewteen 2 cell and morula (25%) diamniotic dichorionic
- Cleave between morula and blastocyst (75%) monochorionic diamnionic
- Cleave after leads to monochorionic and monoamniotic with late cleavage (13 days) leading to conjoined twins
38
Placenta
Fetal portion is cytotrophoblasts (internal and propigate) and synctitotrophoblasts (external and secrete hCG)
Maternal portion is decidua basalis
Lacunae of blood lie in between
39
Cytotrophoblasts
Internal cells that proliferate and give rise to syntitiotrophoblasts. In contact with fetal arteries
40
Synctitiotrophoblasts
- External and come from proliferation of cytotrophoblasts
- In contact with lacunar blood
- Secrete hCG (common alpha with LH, TSH, etc) stimulates corpus luteum to secrete progesterone during first trimester
41
Decidua Basalis
- Maternal component of placenta
| - Contains maternal arteies and veins which dump into lacunae and allow for nutrient exchange
42
Umbilical Cord
- 2 arteries (deoxygenated) and 1 vein (oxygenated)
| - Allantoic Duct
43
Umbilical Arteries
-Come from internal illiac veins and carry deoxygenated blood from fetus
44
Umbilical Vein
-Comes from ductus venosus and carries oxygenated blood to inferior vena cava
45
Allantois
Connects Yolk sac to urogenital sinus, eventually becomes urachus
46
Patent urachus
-excretition of urine out of umbilicus
47
vesicourachal diverticulum
-Diverticulum of bladder
48
Vitelline Duct
-Connects yolk sac to midgut
49
Vitelline Fistula
-Pass meconium through umbilicus
50
Meckels Diverticulum
- Partial obliteration with true diverticulum hanging off ileum.
- May have ectopic gastric or pancreatic tissue
- May lead to melena, pain, volvulus, ulcer
51
1st Aortic Arch
-Gives rise to maxillary artery, which gives rise to middle meningeal which is commonly injured leading to epidural hematoma
52
2nd aortic arch
Stapedial and hyoid artery
53
3rd Aortic Arch
Common Carotid and begining of internal carotid
54
4th Aortic Arch
Gives rise to arch of aorta and right subclavian
55
6th Aortic Arch
Gives rise to begining of pulmonary vasculature and ductus arteriosus
56
Branchial Aparatus
Pharyngeal Cleft: Ectoderm
Arch: Mesoderm
Pouch: Endoderm
57
1st cleft
Ectoderm, external acoustic meatus
58
2nd-4th clefts
obliterated
59
Branchial Cleft Cyst
Failure to obliterate 2-4 arches leads to lateral neck cyst at birth
60
1st Arch
- Mesodermal
- V2 and V3
- Muscles of mastication
- Bones of Jaw
61
Treacher Collins
Failure of development of 1st arch and neural crest cells
| -Leads to jaw hypoplasia and facial abnormalities
62
2nd Arch
-Mesodermal CN7
-Muscles of facial expression
-Some cartilage of lateral hyoid
-
63
3rd Arch
- Mesodermal CN9
- Stylopharyngeus
- Posterior tongue, carotid body and sinus
- Pharyngocutaneous fisutula is persistance of cleft and pouch
64
4th arch
- Mesodermal Superior Laryngeal Nerve X
- Pharyngeal constrictors and posterior tongue
- Cricothyroid
65
6th arch
- Mesodermal Recurrent Laryngeal Nerve
- Intrinsic muscles of larynx
- Posterior Cricoarytenoid is only pharyngeal constrictor that opens folds
66
Recurrent Laryngeal nerve injury
- Surgery (thyroid)
- Hoarsness and difficulty breathing
- Damage to posterior cricoarytenoid limits ability to abduct the chords
67
1st pouch
- endodermal
| - Eustachian Tube and middle ear cavity
68
2nd pouch
Palatine tonsil
69
3rd pouch
Thymus and inferior PTH
70
4th pouch
Superior PTH
71
Digeorge
- Problems with NC and 3rd and 4th pouches
- Absent thymus, PTH
- leads to absent T cells, hypocalcemia
- Tetrology of Fallot
72
Cleft Lip
-Problem with fusion of maxillary prominence and medial nasal prominence
73
Cleft Palate
- Problem with fusion of lateral palatine and medial palatine and may also include nasal septum
- Associated with vitamin A, anti siezures
74
Paramesonephric Duct
- Mullerian duct, present in the female. Inhibited by MIF from sertoli cells
- Becomes fallopian tubes, upper vagina and uterus
75
Bicornate Uterus
- Improper fusion of the paramesonephric ducts
| - Increased risk of miscarriages and unrinary anomalies
76
Mesonephric Duct
- Wolffian duct in males
- Maintained by testosterone
- Becomes Seminal Vesicles, epidydymis, ejculatory duct, and ductus deferens
77
SRY
-Portion of Y chromosome that encodes testes determining factor which induces sertolli cells to secrete MIF and Leydig cells to secrete testosterone
78
Sertolli Cell dysunction
-Leads to reduced MIF and maintenane of both internal strucutres
79
5 alpha reductase deficency
- End organ secretion that converts T to DHT
- Responsible for development of external genetailia and prostate
- Will show as ambigous or female external genetalia with male internal genetalia. At puberty spike in T will allow for appearane of external genetalia
80
Hypospadias
- Urethra on the bottom of the penis caused by failure to close the uethral folds
- Increased risk for UTI
81
Epispadias
- Caused by misplacement of the genital tubercle
| - Associated with extrophy of bladder and other urogenital abnormalities
82
Gubernaculum
Anchors testis to scrotum, disapears in male
| -Is the round ligament and ovarian ligament in females
83
Processus vaginalis
- Location of testis descent
- Patent will cause hydrocele in male
- Obliterated in female
84
Blood Drainage
- Right gonadal diectly into IVC
- Left gonadal into Left Renal then to IVC
- Varicocele more common on left. (RCC-varicocele)
85
Para-aortic nodes
-Testis, ovaries
86
Superficial Inguinal Nodes
- External structures
| - Scrotum, external vagina
87
Hypogastic/obturator nodes
- Internal female strucutres
| - Uterus, cervix, tubes
88
Suspensory Ligament of Ovary
- Anchors ovary to pelvic wall.
| - Contains ovarian vessels
89
Surgical risk of oophrectomy
-Ovarian vessels in suspensoy ligament lie near uretur, so ureter may be accitendally cut
90
Cardinal Ligament of Uterus
- Uterus to pelvic wall
| - Contains uterine vessels
91
Round Ligament
- Uterus to labia majora
| - Remnant of gubernaculum, becomes part of broad ligament. Continuation of Ligament of ovary (also gubernaculum)
92
Ligament of Ovary
- Remnant of gubernaculum, ovary to uterus, then continues in round ligament
- No real function, left over from gubernaculum
93
Broad Ligament
Contains many structures
94
Stratified non keratinized squamous epithelium of female tract
-External structures: Vagina and ectocervix
95
Columnar epithelium
-Internal structures: Endocervix, uterus, tubes
96
Cuboidal Epithelium
- Ovary
| - Secretory function (thyroid, kidneys, eyes only other locations)
97
Male Sexual Response PANS
- Pelvic splanchnics
| - NO to cGMP to Vasodilation leading to errection
98
SANS
- Hypogastric, emission
| - NE to Ca to vasoconstriction to loss of erection
99
Somatic/visceral
-pudendal, ejaculation
100
Sildenafil, vardenafil
-Inhibit cGMP PDE leading to increased erection
101
Spermatagonia
- Produce indefinitely the germ cells
- Located inside Blood Testis Barrier
- Diploid 2N, 2C
102
Primary Spermatocyte
- Duplication of genetic material
| - Diploid (2N 4C)
103
Secondary Spermatocyte
- Divide
| - Haploid (1N 2C)
104
Spermatitid
- Divide
| - Haploid (1N 1C)
105
Spermatogenesis
- Requires large local testosterone concentrations that are maintained by ABP secreted by sertolli cells in response to FSH
- Local T prevents apoptosis
- Exogenous T causes atrophy of leydig leading to decreaed local T levels and azoospermia
106
Blood Testis Barrier
- Maintained by Sertoli cells and basement membrane
| - Protects spermatocytes from autoimmune destruction
107
Sertolli Cell
- Stimulated by FSH to secrete ABP
- Located at the periphery of the seminiferous tubules and nourish spermatogenesis
- Itself secretes inhibin which is negative feedback to hypothalamus and pituitary
- Maintains BTB
- Secrete MIF
- Temperature sensitive, increaased temp (varicocele/cryptorchid) leads to impaired function and decrease inhibin production
108
Leydig Cells
- Produce testosterone, contain 17 hydroxylase to make 17 hydroxy testosterone
- Not temperature sensitive
- Located in the interstitium of the testicle
109
Spermiogenesis
- Transition from spermatid to spermatazoa by losing cytoplasm and gaining tail/acrosome. Occurs in the seminiferous tubules
- Motility is gained in the epidydymis
110
Capacitation
-When sperm are released into the female reproductive tract, Ca, heparin, acidity remove "cap" and allow sperm to fertilize egg
111
Semen
-Prostatic and other fluid that contains Zn, citrate, fructose for energy and buffering functions
112
FSH
- Secreted from basophis in AP
| - Stimulates male sertolli to increase ABP
113
LH
- Secreted from acidophils in AP
| - Stimulates T production in Leydig cells
114
Inhibin B
Secreted from sertolli cells and inhibits FSH
115
Testosterone
- Maintains and matures internal male structures
- 17 hydroxy
- Responsible for secondary male sex characteristics
- Conveted to Estrogen by aromatase (fat cells and growth plates)
- Converted to DHT by 5 alpha reductase
116
DHT
- Stronger testostrone, converted in peripheral tissues
- Impt for external genetailia and secondary sex characteristics.
- Inhibited by finasteride
117
Estrogen
- Estrone produced by aromitazation in adipose tissue
- Estradiol produced by Ovary
- Estriol produced by placenta during pregnancy. (Decreased in IUGR and placental problems)
118
Estrogen Receptor
- Mostly nuclear and regulate transcription
| - Some new found receptors are GPCR
119
Estrogen Functions
- Increase Endometrial proliferation
- Stimulate PRL release but inhibit milk letdown (Breast development during pregnancy but no ovulation until removal of estrogen at birth)
- Secondary female sex characteristicss
- Increase Myometrial Excitabiltiy (opposed by progesterone)
- Increase production of binding globulins and also increase HDL and reduce LDL
120
Estrogen Production Ovary
- Theca cells are stimulated by LH which leads to activation of desmolase and increased andro production which diffuses to granulosa cells
- Granulosa cells are stimulated by FSH to increase aromatase activity and convert andro to estradiol
121
LH Spike
- FSH inreases LH receptors and Estrogen production which flips from negative feedback to positive by increasing GnRH receptors in hypothalamus
- During follicular phase, at begining of luteal phase progesterone is secreted which shuts off GnRH production
122
Progesterone
- Produced by Corpus Luteum and produced during luteal phase of menstrual cycle
- Later produced by placenta
- Maintains pregnancy
- Increases endometrial secretions and spiral artery development
- Decreases GnRH production and prevents ovulation
- Decreases Estrogen receptor sensitivity
- Decreases myometrial contractility and preserves pregnancy
- Thickens cervical mucus inhibiting sperm penetration and increasing zygote receptivity
- Increase Body temperature (marked as time of ovulation.
123
Tanner Stage I
Child nothing
124
Tanner Stage 2
Pubic hair appears but is sparse and colorless. Pubarche and Thelarche
125
Tanner Stage 3
Darkening of pubic hair and growth of secondary sex characteristics
126
Tanner Stage 4
Continued growth and achievment of adult size. Aereola still raised
127
Tanner 5
Adulthood, growth stops and aereola no longer rasied.
128
Oogenesis
- 1 oocyte (2N, 4C) Arrested in prophase 1 until ovulation occurs, polar body extruded at ovulation
- 2 oocyte (1N, 2C) arrested at metaphase 2 until fertilization
- Ovum 1N, 1C
129
Graffian Follicle
- Dominant follicle is determined by the number of FSH receptors and increased E2.
- Theca that secrete andro are on outside
- Ganulosa that convert to E2 are on inside
130
Physiologic Changes of Pregnancy
- Hypervolemic and Hypoosmolar state, change in setpoint of OVLT in hypothalamus, Increaesed HR and often decreased BP
- Physiologic anemia from hemodiulation
- Progesterone has anti cortisol properties, anti immune properties, and vasodilatory (smooth muscle relax) properties
- Hyperventalation and respiratory alkalosis
131
Fertilization
Must occur in 24 hrs, most commonly occurs in ampula
| -cortical granules are released to prevent polyspermy
132
Implantation
Occurs within 6 days of fertilization and is aided by progesterone thickening of mucus and proliferation
-Implantation occurs at blastocyst stage
133
Lactation
PRL secreted throughout pregnacy because of estrogen
- At delivery progesterone and estrogen are removed which allows for milk let down
- Suckling stimulates PRL and Oxytocin production and maintenance of lactation
134
Oxytocin
- Created in hypothalamus (supraoptic and paraventricular)
- Stored in Post Pit
- Stimulates smooth muscle relaxatoin and is important in partruition and lactation
135
Sheehans Syndrome
Infarction of AP secondary to hypovolemic ischemia
| -most commonly presents as inability to lactate
136
hCG
- Common alpha subunit with LH, FSH, TSH
- Secreted by synctitotrophoblasts to maintain CL
- Elevated in hyatidaform moles and choriocarcinomas
- Also increased in Downs
137
HPL
- GH of pregnancy raises blood sugar, may be physiologic glycosuria.
- Also stimulates breast development
138
Fetal Hgb
-Decreased affinity for 2,3 BPG which increases O2 binding leading to transfer from maternal to fetal blood
139
ABO mismatch
IgM so no crossing palcenta, may lead to jaundice
140
Rh mismatch
-IgG crosses placenta
141
Increased AFP
Open fetal cavity
142
Oligohydramnios
Renal problem
143
Polyhydramnios
Swallowing problem
144
Decreased AFP
Downs, Edwards
145
Decreased hCG
Edwards, increased in Downs
146
Decreased PaPP-1
Patau (also nuchal lucency)
| -Increased in Downs with nuchal lucency
147
Klinefelters
- 47 XXY, most commonly caused by maternal nondisjunction during meosis I or II. Barr body present
- Tall eunichoid body shape with female hair distribution and gynecomastia
- Fibrous replacement of seminiferous tubules
- Decreased Test, increased E, increased FSH and LH. Decreased Inhibin
148
Turners Syndrome
- 45 XO, or more commonly 46XX with significant X silencing and Mosacism. May have varying degrees of severity. Paternal nondisjunction
- Streak gonads leading to deficent E and T production with increased FSH and LH
- Lymphadenopathy, especially cystic hygroma of neck
- Bicuspid aortic valve and aortic coarctation
- Horseshoe Kidney
- increased Risk of Hashimotos thyroiditis
- Diabetes
- Vision problems and mild cognitive impairment
- Remove ovary because of risk of dysgerminoma
149
Noonan Syndrome
-Presents with many similar features to Turners but is caued by mutation in RAS MAPK pathway
150
Androgen Insensitivty
- Leads to male pseudohermaphrodite (XY) with absent female external genetalia and lack of secondary sex characteristics
- AR is present on X chromosome and dysfunction is related to the number of CAG repeats
- Increased T, E, LH with decreased FSH (AR dysfunction in pituitary shortcuts negative feedback)
151
5 Alpha reductase deficency
- Converts T to more powerfult DHT. T necessary for growth of internal structures and DHT for external structures
- Leads to normal internal and ambigous or female external strucutres.
- Will become masculinized at puberty due to surge in testosterone
- AR inheritance
- All hormone levels will be normal except for DHT
152
Female Pseudohermaphrodite
- Caused by exposure to androgens in utero
- Normal internal female with virulization of external structures and secondary sex characteristics
- CAH 11/21 are common causes.
- Also caused by exogenous androgens
153
Kallman Syndrome
- Impaired migration of GnRH neurons and olfactory neurons
- Anosmia
- Absence of GnRH from hypothalamus leads to decrease in all gonadotrophs and sex hormones.
154
Hyatidaform Mole
- Cystic swelling of Villi with proliferation of trophoblasts leading to increased HCG production
- Treated with D and C with methotrexate
- Monitor hCG levels for recurrence and treatment success
- May progress to choriocarcinoma, more commonly complete (responds to chemo while the ovarian form does not)
- May present with abnormal bleeding, passage of grapelike material (villous and trophoblasts) and abnormally increased bHCG and abnormally enlarged uterus
- May present with pre-eclampsia in first trimester
155
Complete Mole
- Ovum with no genetic material is fertilzed by sperm that generally subseauenty divides (endoduplication)
- 46x(xy)
- Complete absence of fetal tissue, edematous villi with massive trophoblastic proliferation leading to massive increased in bhCG
- Also causes severe uterine distension that may cause rupture, more common in complete
- May progress to choriocarcinoma (more common in complete)
156
Partial mole
- Normal ovum that is fertalized by 2 sperm or from endoduplication of single sperm.
- 69 chromosomes
- There is the presence of some fetal tissue, bHCG will not be elevated as much, there will be less trophoblastic proliferation, there will be less uterine distension, and conversion to choriocarcinoma is more rare.
157
Mullerian Agenesis
- Mullerian abnormalities that occur independent of ovarian development
- Normal secondary sex characteristics with primary amenorrhea
158
Pre-Eclampsia
- Impairment of placental maternal interface leads to fetal insuficecny leading to release of vasoconstrictive factors systemically in the mother
- Impaired dilation of spiral arteries leads to fetal ischemia and release of vasoactive factors
- Causes HTN, Proteinuria, Edema after 20 weeks. Before 20 weeks-molar pregnancy
- Commonly presents with headaches, mental status changes, blurred vision, edema
- Pulmonary edema and thrombocytopenia
- Fibrinoid necrosis may be present with very high HTN
- Death may come from cerebral hemorrhage or ARDS
- Tx: delivery of baby, hhydralazine, nifedipine (Do not give ACEI)
- Risk Factors: Nulliparity, DM, renal disease, HTN, Obesity, lupus anticoagulant
159
HELLP
- In the context of pre-eclampsia get micropangiopathic hemolytic anemia in vasculature of liver
- May cause liver infarction and damage
- Hemolytic anemia (schistocytes), Elevated Liver enzymes, Low Platelets
- May cause ARDS, or DIC/bleeding
- Will also see increase LDH, hyperuricemia, etc
160
Eclampsia
- If pre-eclampsia and HTN are accompanied by siezures
| - Treat with magneium sulfate and deliver baby
161
Abruptio Placenta
- Preterm detachment of placenta from decidua basalis
- Painful vaginal bleeding in the third trimester
- Requires immediate delivery of baby, high risk of stillbirth and bleeding from mother
- May cause DIC
- Increased risk with smoking, HTN, and cocaine usage
162
Placenta Acreta
- Placenta attaches to the myometrium because of absence of endometrium (often caused by overexuberrant D and C)
- Difficulty delivering placenta after birth and massive bleeding, may require hysterectomy or be fatal to mother
- Increased risk with C-section, placenta previa, inflammation
163
Placenta Previa
- Placenta attaches over the cervical os
- Will present with painless bleeding at any time during pregnancy
- Requires C-Section delivery
- Increased risk with C-Section or multiparity
164
Retained Placental Tissue
May cause increased bleeding risk and risk of infection with staph aureus
165
Ectopic Pregnacny
- Most common site it the fallopian tube
- Presents with sudden abdominal pain with a HCG level that is elevated less than expected. Often presents in the context of amenorrhea
- Surgical emergency because of risk of rupture
- Endometrium will be decidualized with lacunae and dilated spiral arteries but there will be an absence of villi
- Risks: PID, any form of tubal scarring or surger, endometriosis
166
Polyhydramnios
- Excessive amniotic fluid
| - Most commonly caused by swallowing impairment (anencephaly, duodenal, esophageal atresia)
167
Oligohydramnios
- Too little amniotic fluid
- Usually caused by an inability to pass urine by fetus
- Renal agenesis, posterior urethral valve, placental insufficency
- May end up with congential malformations and potters sequence
168
Potter sequence
-Lung hypoplasia and facial/limb abnormalities associated with oligohydramnios
169
Congenital Toricolus
-Associated with IUGR and Potter sequence
170
Posterior Urethral Valves
- Only seen in males and is caused by impairment of wolffian duct formation through prostate
- Causes oligohydramnios and potter sequence
- May cause bladder wall thickening and hydronephrosis leading to renal failure at birth
171
Amniotic embolism
-DOE at labor, see squamous cells in embolism
172
Hemolytic Disease of newborn
- Edema and anemia in child
- Seen with Rh incompatability because IgG can cross the placenta but IgM can't
- Hydrops Fetalis
173
Hydrops Fetalis
-Any time there is fluid in 2 or more spaces in fetus
-Pleural, pericardial, ascites, edema, etc
-Associated with alpha thal, hemolytic newborn, TORCH,
Turners, Cardiac Anomalies
174
Cervical Dysplasia (CIN)
- Almost always associated with HPV high risk (16, 18, 31, 33) (6, 11) cause condyloma
- HPV infects basal layers near ecto/endo junction. E6 inhibits p53 (p21, decrease BCL-2) and E7 inhibits Rb (release E2F and allow G1 to S progression)
- Dysplasia not extending through all layers is reversible and CIN. Once all layers is CIS
- Squamous is ectocervix and adeno is endocervix
- Pap smear is most succesful cancer screening tool and can catch cervical if sample from junctional area.
- Koilocytes with increased nuclear to cytoplasmic ratio are the cells that can cause problems
175
Cervical cancer
- Consequence of CIN (most squamous and ecto)
- Spreads locally with most commonly into ureters or bladder causing hydropnephrosis and acute renal failure leading to death.
- An Aids defining illness as majority of HPV infections cleared and don't progress to cancer
- Increase risk with HIV, smoking, multiple early sex partners
- Gardasil vaccine is recombinant
176
Cervicitis
-Associated with loss of low pH and loss lactobacillus
177
Endometritis
- Associated with retained products of conception or IUD
| - Staph aureus commonly and anaerobes, treat with clinda/gentamycin
178
Endometriosis
- Endometrial tissue not located in uterus
- Causes painful cycle related peritoneal and pelvic pains
- Pain with intercourse and defecation
- May lead to choclate cysts and tubal scarring leading to infertility
- Tx: NSAIDs, OC, Leuprolide, Danazol
179
Adneomyosis
- Presence of endometrial tissue in the myometrium
- Painful and enlarged uterus
- Tx: hysterectomy
180
Endometrial Hyperplasia and cancer
- Caused by increased estrogen exposure and is precursor to endometrial cancer
- May present with abnormal bleeding
- Associated with unopposed estrogen (tamoxifen), nulliparity, granulosa tumor, PCOS, hormone replacement, obesity, diabetes
- Prognostic sign is degree of myometrial invasion and tends to invade locally
181
Endometrial polyps
-Benign grwoths that are common and may cause post menopausal bleeding
182
Asherman's syndome
- Secondary amenorrhea due to loss of decidual layer (Stem cells)
- Often complication of D and C
183
Vaginal Cancer
- Most commonly SCC and is related to high risk HPV
- May also have melanoma (S 100+)
- Extramammary pagets disease (PAS and keratin +)
- Drainage of lower 1/3 goes to superficial nodes and upper 2/3 goes to hypogastric nodes
184
Vaginal Adenosis
- Persistant of glandular epithelium in vagina. Associated with DES use in utero (Mother may increase risk of breast cancer)
- May progess to clear cell carcinoma (adeno)
185
Embryonal Rhadomyosarcoma
- Rare grapelike tumor of girls less than 5 years
| - immature skeletal muscle rhabdomyoblasts
186
Leiomyoma
- Very common benign tumor of smooth muscle that is sensitive to estrogen and will dissapear in menopause (If present post menopausal think cancer)
- White whorled, well circumscribed masses
- Commonly causes bleeding and may cause pain and miscarriages
- increased incidence in blacks
- Does not progress to cancer
187
Leiomyosarcoma
- Malignant tumor of smooth muscle in uterus most commonly arising post menopausally
- Arises de novo
- Hemorrhagic necrosis
- May cause postmenopausal bleeding and commonly recurs after removal
- Tends to spread locally
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Premature ovarian failure
- Menopause (increased FSH and decreased estrogen) prior to 40 years of age.
- Loss of follicles and cells that produce estrogen
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PCOS
- Caused by increased LH leading to excess androgen release from ovaries that shuts down FSH production and prevents ovulation.
- Anovulation leads to the production of cysts
- Insulin resistance is also a halmark of the disease and increases the production of androgens from the ovary
- Obesity is also a halmark with fat tissue converting testosterone to estrogen to inhibit the HPA
- Labs: Increased LH, Test, Estrogen with reduced FSH
- Presntation: DM2 (insulin resistance) acne, obesity, hirsuitism, amenorrhea, cystic ovary
- Hyperestrogen and absent progesterone (absence of luteal phase) state leads to endometrial proliferation and hyperplasia that increases risk for endometrial carcinoma
- Tx: OC and medroxyprogesterone to shut down HPA, spironolactone blocks androgenic (acne, hirsuitism), metformin for DM
- Can give clomifene for infertility: SERM that inhibits GnRH gonadrop receptors meaning no negative feedback and increased LH and FSH production.
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Follicular Cyst
- unruptured follicle. Very common, especially with abarent anovulatory cycles
- Leads to hyperestrogen and low progesterone state that may cause endometrial hyperplasia and abnormal uterine bleeding
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Corpus Luteum Cyst
-Blood in corpus luteum, inconsuquental
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Theca-Leutin Cyst
- Multiple straw color fluid filled cysts.
- Occur because of massive HCG stimulation
- Seen with twins+ or molar pregnancies
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Dermoid Cyst
-Mature teratoma that is almost always benign. Rare chance of SCC from Squamous component of teratoma.
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Endometrial Cyst
- Endometrial tissue in ovary (endometriosis) causes pain with menstraul cycle
- Choclate cyst.
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Ovarian Carcinoma Overview
- Tumor marker is CA-125. Not used as a screening tool, but can be used to monitor progression.
- BRCA and HNPCC have increased risk of tumors, especially serous cystadenocarcinoma
- Germ Cell (Yolk Sac, Teratoma, choriocarcinoma, dysgerminomma, strumma ovarii)
- Surface: Serous and mucinous cystadenocarcionoma
- Sex Chord Stroma: Fibroma, Granulosa, Brenner
- Metastasis: Kruckenberg and others
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Dysgerminoma
- Rare germ cell tumor in females. Common in males. Presents as large sheets of uniform cells
- Increased risk with pseudohermaphroditism and Turner syndrome
- Marker is PLAP, LDH and molderate hCG
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Choriocarcinoma
- Malignant proliferation of trophoblasts. Villi will be absent.
- Massive increase in hCG that could lead to the formation of Theca-Leutin Cysts
- Hearly hematogenous metastasis to lungs
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Yolk Sac (Endodermal Sinus)
- Most common tumor of kids.
- AFP is tumor marker
- Aggressive tumor with schiller duval bodies (glomeruli appearing bodies)
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Teratoma
- Mature teratoma is not malignant and is called a dermoid cyst. Can be malignant rarely if part becomes malignant SCC.
- Contains tissue from multiple germ layers
- Immature is rare but aggressive
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Struma Ovarii
-Teratoma that produces thyroid and presents as hyperthyroidism in mother
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Serous Cystadenoma
- 45% of surface tumors (Cuboidal cells) appears like fallopian tube
- Benign and can be bilateral
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Serous Cystadenoarcinoma
- 45% of surface tumors. Malignant. Increased risk with BRCA.
- Papillary projections and psammoma bodies
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Mucinous Cystadenoma
-Mucin containing benign tumor
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Breast
- Modified sweat gland that develops under the influence of estrogen and can develop anywhere along milk line (axilla to vulva)
- Functional unit is terminal duct/lobular unit. Lobules produce milk and ducts transport
- 2 Epithelial layers the luminal which produce milk and basallar (myoepithelial) that squeeze it out.
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Acute Mastitis
- Infection and inflammation just below the aereola.
- Most commonly effects women who are breast feeding and is most commonly staph auereus
- Differentiate from inflammatory carcinoma by response to antibiotics
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Fat Necrosis
- Trauma to the breast leads to fat necrosis and subsequent soppnification.
- Will be calcified and may produce a mass on examinaition
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Gynecomastia
- Development of breasts in males, caused by elevated estrogen and reduced testosterone
- Commonly seen in adolescents, elderly, and Klienfelters (increased risk for breast Cancer)
- Also seen in cirrhosis
- Male breast cancer rare and associated with BRCA-2 mutations
- Drugs (spironolactone, ketocolanazole, digitalis, alcohol)
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Fibrocystic Change
- Rarely produce a mass and are often inceidental
- Hold a minimal risk of cancer
- Occur in TDLU
- Present as multiple small lesions that are hard in PREMENOPAUSAL women.
- Often responsive to estrogen
- Increased risk with atypical hyperplasia
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Sclerosing Adenosis
- Increase number of acini in lobules and may be calcified
| - Not cancer, and carries low risk.
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Epithelial Hyperplasia
- Can occur in lobules, but more commonly in ducts.
- More than 2 cell layers deep, but rarely atypical.
- Atypia increases risk of cancer
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Fibroadenoma
- Most common benign tumor in premenopausal women
- Caused by proliferation of stromal cells
- Presents as a mobile, rock hard, usually unilateral mass
- Responsive to estrogen, so grows with menstruation/pregnancy and shrinks with menopause
- No risk of cancer
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Intraductal Papilloma
- Papillary projection into the duct, commonly just below the nipple
- Often presents as bloody or serous discharge
- May be calcified because of papillary nature on mammography.
- Will still contain epithelial coating and is normally not associated with malignancy
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Phyllodes Tumor
- Most common non malignant tumor in postmenopausal women
- Proliferation of stroma with a leaf like appearance
- Often a large bulky mass and is rarely malignant
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Malignant Breast Cancer
- Most common in post menopausal women. If premenopausal, think of a syndromic case (BRCA)
- Risk is tied to estrogen exposure (late menopause, nulliparity)
- Gentic cases most commonly tied to BRCA mutations (medullary)
- Expression of ER, PR, and Her2-neu (EGFR) are important in prognosis and treatment
- Treatment of ER/PR positive with Tamoxifen (SERM)
- Treatment of Her2-Neu with traztuzumab a mab to EGFR
- Triple negative is poor prognosis and most commonly seen in african american women
- Metastasis is most severe factor (bone and brain)
- Lymphatic invasion is most useful
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DCIS
- By far most common 75%+
- Malignant growth of epithelial cells into the duct but no invasion of the BM
- Most commonly comedotype which can have necrosis and calcifications in center
- Calcifications and masses picked up on mammography
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Paget's Disease
-DCIS or in situ cells that move out of the nipple and cause an eczematous reaction around the nipple
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Medullary
-Most commonly seen in BRCA and has a good prognosis
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Inflammatory
- Invasion of dermal lymphatics leads to blockage of lymph outflow and inflammation
- Present with peau de orange, nipple retraction and inflammation
- Poor prognosis
- Differntiate from acute mastitis by response to antibiotic treatment
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LCIS
- Malignant growth of lobular epithelial cells that don't invade through basement membrane
- Commonly incidental finding and is commonly bilateral
- Minimal risk of invasion through BM, but demonstrates increased estrogen exposure and elevated overall risk
- Generally treated with tamoxifen and close monitoring
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Invasive Lobular
- Invasion of malignant cells of lobule
- Lack E-Cadherin and invade in a single file line
- Lesions are commonly bilateral
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Prostate
- Develoment from urogenital sinus is driven by DHT in utero
- Contains dense stroma and glandular structures that secrete an alkaline Zn, citrate rich fluid to buffer and nourish sperm
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Prostatitis
- Most commonly bacterial (GC younger, E Coli/Pseudomonas older)
- Can be abacterial with lymphocytes present on urinalysis
- Will present as tender boggy prostate on DRE
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Orchitis
- STD bugs can do it
| - Also mumps can do it and lead to infertility if it occurs after age of 12 years
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Benign Prostatic Hyperplasia
- DHT driven hyperplasia and differentiation of fibrous and glandular tissue in the periurethral zone.
- Glandular structures not atypical and carries no risk of adenomcarcionoma
- Androgens increase local FGF leading to proliferation of fibrous tissue
- Proliferation is often nodular
- PSA can be used to monitor
- Mainly causes urinary symptoms and can lead to backup. Bladder hypertrophy and diverticula are possible complications.
- Can progress to post renal azomtemia and renal failure with hydronephrosis
- Tx: Finasteride decreases androgen production and grwoth
- Tamsulosin is specific alpha 1a and only effects urinary symptoms. Tarazosin and prazosin are alpha 1 antagonists that also effect vasodilation
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Prostate Adenocarcinoma
- Adenocarcinoma of glandular tissue not related to BPH
- Increase in gland number and decrease in gland size with atypia.
- Occurs in peripheral zone, can be felt on DRE
- Can be monitored with PSA but a biopsy is necessary for diagnosis. PAP also used.
- Biopsy will show single cell layer not 2.
- Increase risk for african americans and is related to AR and DHT exposure
- Commonly metastasizes to lumbar spine generating osteoblastic sclerotic lesions. Leads to elevation is serum ALk Phos.
- Tx: Surgical resection, Flutamide is AR blocker and leuprolide is GnRH agonist that when given continously shuts off gonadotropins.
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Cryptorchidism
- Impaired descent of testis and are stuck in abdominal cavity. Driven by MIF and Testosterone
- Can be surgically corrected. If not has complications
- Seminoma is increased
- Infertility and death/fibrosis of sertolli cells and seminiferous tubules
- Decresed inhibin, increased FSH and LH generally normal testosterone, Leydig cells are not as temperature responsive.
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Varicocele
- Dilation of veins in the pampinaform plexus. Leads to bag of worms on physical exam.
- Most common on the Left vein due to drainage into the Left gonadal vein instead of IVC
- Associated with spread of RCC
- May cause infertility because of increased temperature.
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Hydrocele
- Accumulation of clear fluid in the scrotum
- Occurs due to patency of tunica vaginalis (young and old)
- Can be transiluminated
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Penile SCC
- Most commonly caused by high risk HPV 16, 18, 31, 33
- Increased risk with non circumscised. Shmegma is inflammatory and increases risk.
- Often presents as precursor leukoplakia on shaft and erythroplakia on glans of penis
- Will metastasize to superficial inguinal nodes
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Peyronies
- Fibrosis of the tunica albuginea leading to uncomfortable penile formation.
- Associated with deputrynes contracture and otosclerosis
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Priapism
- Long time unprovoked erection.
- Sickle cell, Trauma, drugs
- Trazadone!
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Testicular Tumors
- Most commonly occur in younger men, 15-35 and present as painless enlarging testicle.
- If older man think lymphoma
- Do not biopsy, remove because 95% are malignant and biopsy can seed
- Spread to para-aortic lymph nodes
- Majority of germ cell tumors are mixed and can have presentation of both components.
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Seminoma
- Most common germ cell tumor
- Sheets of uniform clear cells with pale cytoplasm
- Increased risk in cryptorchidism
- Not aggressive and generally responds to radio-treatment
- Marker is PLAP
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Yolk Sac
- Most common tumor of young children
- Yellow mass that secretes AFP
- Schiller-Duval bodies with glomeruloid appearance
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Choriocarcinoma
- Tumor of trophoblasts, secretes hCG and spreads rapidly hematogenously, most commonly to lungs
- Patient may present with gynecomastia because of hCG similiarity to LH
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Teratoma
- Rare tumor, but most commonly malignant in males (in contrast to females)
- Multiple germ layers and may secrete a number of markers
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Embryonal Carcinoma
- Mixed tumor of multiple germ cell tumors
- Painful with glandular or papillary morphology
- Markers most commonly AFP and HCG
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Leydig tumor
- Sex chord/stromal tumor, secretes androgen
- Reinke crystals will be present
- Commonly presents with gynecomastia
- Sertolli tumor is hormonally silent
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Lymphoma
- Think of lymphoma in an older man (greater than 40 yrs)
- Most often DLBCL and is a secondary from other metastasis.
- Aggressive with poor prognosis
