Steve Avery's Reproductive Lockup Flashcards Preview

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Flashcards in Steve Avery's Reproductive Lockup Deck (287):
1

Sonic headgehog gene

Produced at the base of the limbs in zone of polarizing activity;
involved in patterning along anterior-posterior axis;
Involved in CNS development;
Mutation can cause holoprosencephaly

2

Wnt-7 gene

Produced at the apical ectodermal ridge (thickened ectoderm at distal end of each developing limb);
Necessary for proper organization along dorsal-ventral axis

3

FGF gene

Produced at the apical ectodermal ridge;
stimulates mitosis of underlying mesoderm;
providing for lengthening of limbs

4

Homeobox (Hox) genes

Involved in segmental organization of embryo in a craniocaudal direction. Hox mutations lead to appendages in wrong locations

5

Early fetal development: day 0

Fertilization of egg by sperm forming the zygote, initiating embryogenesis

6

Early fetal development: within 1 week of fertilization

hCF secretion begins around the time of implantation of the blastocyst

7

Early fetal development: within 2 weeks of fertilization

bilaminar disc (epiblast and hypoblast);
2 weeks= 2 layers

8

Early fetal development: within 3 weeks of fertilization

trilaminar disc, 3 weeks=3 layers;
gastrulation;
primitive streak, notochord, mesoderm and its organization, and neural plate begin to form

9

Early fetal development: weeks 3-8 post fertilization

Embryonic period;
neural tube formed by neuroectoderm and closes by week 4;
organogenesis;
extremely susceptible to teratogens

10

Early fetal development: Week 4

Heart begins to beat;
upper and lower limb buds begin to form;
4 weeks= 4 limbs

11

Early fetal development: week 6

Fetal cardiac activity visible by transvaginal ultrasound

12

Early fetal development: week 10

Genitalia have male/female characteristics

13

Grastrulation

Process that forms the trilaminar embryonic disc;
Establishes the ectoderm, mesoderm, and endoderm germ layes;
starts with the epiblast invaginating to form primitive streak

14

Surface ectoderm leads to what notable structures

Adenohypophysis (from Rathke pouch);
lens of the eye;
epithelial lining of the oral cavity, sensory organs of ear, and olfactory epithelium;
Epidermis;
anal canal below the pectinate line;
parotid, sweat, and mammary glands

15

Craniopharyngioma

Benign Rathke pouch tumor with cholesterol crystals, calcifications

16

Neuroectoderm leads to what notable structures

Brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland), retina, optic nerve, spinal cord;
Just think CNS

17

Neural crest leads to what notable structures

PNS (dorsal root ganglia, cranial nerves, celiac ganglion, Schwann cells, ANS);
Melanocytes;
chromaffin cells of adrenal medulla;
Parafollicular C cells of thyroid;
pia and arachnoid;
bones of the skull;
Odontoblasts;
aorticopulmonary septum

18

Mesoderm leads to what structures

Muscle, bone, connective tissue, serous linings of body cavities(e.g. peritoneum), spleen (from foregut mesentery), cardiovascular structures, lymphatics, blood, wall of gut tube, vagina, kidneys, adrenal cortex, dermis, testes, ovaries;

19

Notochord induces ectoderm to form neuroectoderm (neural plate). Its post natal structures are

Nucleus pulposus of the intervertebral disc. That is it.

20

Endoderm

Gut tube epithelium (including anal canal above the pectinate line), most of urethra (derived from urogenital sinus), luminal epithelium derivatives (e.g. lungs, liver, gall bladder, pancreas, eustachian tubes, thymus, parathyroid, thyroid follicular cells)

21

Errors in morphogenesis: agenesis

Absent organ due to absent primordial tissue

22

Errors in morphogenesis: aplasia

Absent organ despite presence of primordial tissue

23

Errors in morphogenesis: Hypoplasia

Incomplete organ development;
primordial tissue present

24

Errors in morphogenesis: Deformation

extrinsic disruption;
occurs after the embryonic period

25

Errors in morphogenesis: Disruption

secondary breakdown of a previously normal tissue or structure (e.g. amniotic band syndrome)

26

Errors in morphogenesis: malformation

Intrinsic disruption;
occurs during embryonic period (weeks 3-8)

27

Errors in morphogenesis: sequence

Abnormalities result from single primary embryologic event (e.g. oligohydramnios leads to potter sequence)

28

Teratogen and its effect: ACE inhibitors

Renal damage

29

Teratogen and its effect: Alkylating agents

absence of digits, multiple abnormalities

30

Teratogen and its effect: Aminoglycosides

CN VIII toxicity;
a mean guy hit the baby in the ear

31

Teratogen and its effect: Carbamazepine

Neural tube defects, craniofacial defects, fingernail hypoplasia, developmental delay, IUGR

32

Teratogen and its effect: Diethylstilbestrol (DES)

Vaginal clear cell adenocarcinoma, congenital Mullerian anomalies; Adenosis (persistance of columnar cells in upper 2/3 of vagina, should be replaced by squamous cells) which leads to Vaginal clear cell adenocarcinoma

33

Teratogen and its effect: Folate antagonists

Neural tube defects

34

Teratogen and its effect: Lithium

Ebstein anomaly (atrialized right ventricle)

35

Teratogen and its effect: Methimazole

Aplasia cutis congenita ("Congenital absence of skin")

36

Teratogen and its effect: Phenytoin

Fetal hydantoin syndrome: microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR, intellectual disability

37

Teratogen and its effect: Tetracyclines

Discolored teeth; Teethracyclines

38

Teratogen and its effect: Thalidomide

Limb defects (phocomelia, micromelia-flipper limbs;
limb defects with tha-limb-domide

39

Teratogen and its effect: valproate

Inhibition of maternal folate absorption leading to neural tube defects;
Valproate inhibits folate absorption

40

Teratogen and its effect: warfarin

Bone deformities, fetal hemorrhage, abortion, opthalmologic abnormalities;
Do not wage war on the baby, keep it heppy with heparin (does not cross placenta)

41

Teratogen and its effect: Alcohol

Common cause of birth defects and intellectual disability; fetal alcohol syndrome

42

Teratogen and its effect: cocaine

Abnormal fetal growth and fetal addiction; placental abruption

43

Teratogen and its effect: Smoking (nicotine, CO)

A leading cause of low birth weight in developed countries;
Associated with preterm labor, placental problems, IUGR, ADHD

44

Teratogen and its effect: Iodine (lack of or excess)

Congenital goiter or hypothyroidism (cretinism)

45

Teratogen and its effect: Maternal diabetes

Caudal regression syndrome (anal atresia to sirenomelia);
congenital heart defects;
neural tube defects

46

Teratogen and its effect: Vitamin A excess

Extremely high risk for spontaneous abortions and birth defects (Cleft palate, cardiac abnormalities)

47

Teratogen and its effect: X-rays

Microcephaly, intellectual disability

48

Fetal alcohol syndrome

One of the leading causes of congenital malformations in the US;
Increased risk for: intellectual disability, pre and postnatal developmental retardation, microcephaly, holoprosencephaly, facial abnormalities (smooth philtrum, thin upper lip, small palpebral fissures, hypertelorism), limb dislocation, and heart defects

49

Dizygotic twins arise from

Arise from 2 separate eggs fertilized by 2 separate sperm;
have 2 separate amniotic sacs;
2 separate placents (chorions).

50

Monozygotic twins arise from

arise from 1 fertilized egg that splits into 2 zygotes in early pregnancy

51

Monozygotic twins that separate in the first 4 days

before morula forms;
cleavage can cause fused or separate placenta;
either way you get dichrorionic and diamniotic placenta;

52

Monozygotic twins that separate in the 4-8 day range

(after morula forms, but before blastocyte);
Cleavage leads to monochorionic diamniotic twins

53

monozygotic twins that separate in the 8-12 day range

After blastocyst forms;
get monochorionic monoamniotic twins

54

Monozygotic twins that separate after 12 days

Cleavage leads to monochorionic monoamniotic conjoined twins

55

Fetal component of placental: cytotrophoblast

inner layer of chorionic villi;
Cytotrophoblast makes Cells

56

Fetal component of placental: Syncytiotrophoblast

Outer layer of chorionic villi;
secretes hCG (structurally similar to LH; stimulates corpus luteum to secrete progesterone during first trimester)

57

Maternal component of placental: Decidua basalis

Derived from the endometrium, the maternal blood would be in the lacunae

58

Umbilical cord

contains 2 umbilical arteries (look like the eyes): return deoxygenated blood from fetal internal iliac arteries to placenta;
Contains 1 umbilical vein (looks like the mouth): supplies oxygenated blood from placenta to fetus, drains into IVC via liver or ductus venosus;
Arteries and veins are derived from allantois

59

Urachus

In the 3rd week the yolk sac forms the allantois, which extends into the urogenital sinus. Allantois becomes the urachus, a duct between fetal bladder and yolk sac

60

Failure of urachus to obliterate causes

Patent urachus- urine discharge from umbilicus;
Urachal cysts- partial failure of urachus to obliterate, fluid-filled cavity lined with uroepithelium, between umbilicus and bladder, can lead to infection and adenocarcinoma;
Vesiourachal diverticulum- outpouching of bladder

61

Vitelline duct

7th week-obliteration of vitelline duct (omphalo-mesenteric duct), which connects yolk sac to midgut lumen;

62

Failure of the vitelline duct to obliterate causes

Vitelline fistula- meconium discharge from umbilicus;
Meckel diverticulum- Partial closure, with patent portion attached to ileum (true diverticulum). May have ectopic gastric and pancreatic tissue leading to melena, periumbilical pain, and ulcers

63

What arterial system does this aortic arch develop into: 1st arch

Part of the maxillary artery (branch of external carotid);
1st arch is the max

64

What arterial system does this aortic arch develop into: 2nd arch

Stapedial artery and hyoid artery;
Second=Stapedial

65

What arterial system does this aortic arch develop into: 3rd arch

Common Carotid artery and proximal part of internal Carotid artery;
C is 3rd letter

66

What arterial system does this aortic arch develop into: 4th arch

on left-aortic arch;
on right-proximal part of right subclavian artery;
4th arch=4 limbs=systemic

67

What arterial system does this aortic arch develop into: 6th arch

Proximal part of the pulmonary arteries and ductus arteriosis (on left only);
6th=pulmonary and pulmonary to systemic shunt

68

Branchial apparatus

AKA pharyngeal apparatus;
composed of clefts, arches, pouches;
Clefts-derived from ectoderm, AKA branchial grooves;
Arches-derived from mesoderm (muscles, arteries) and neural crest (bones, cartilage);
Pouches- derived from endoderm;
CAP covers inside to outside= Clefts, Arches, Pouches

69

Branchial cleft derivates

1st cleft develops into external auditory meatus;
2nd through 4th clefts form temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme;
Persistent cervical sinus leads to branchial cleft cyst within lateral neck (remnant of 2nd cleft)

70

Branchial arch derivatives of 1st arch

Cartilage: Meckel cartilage (Mandible, Malleus, incus, spheno-Mandibular ligament;
Muscles: Muscles of Mastication (temporalis, Masseter, lateral and medial pterygoids), Mylohyoid, anterior belly of digastric, tensor tympani, tensor veli palatini;
Nerves: CN V2, V3 (chew);

71

Branchial arch derivatives of 2nd arch

Cartilage: Reichert cartilage (Stapes, Styloid process, lesser horn of hyoid, Stylohyoid ligament);
Muscles: Muscle of facial expression )Stapedius, Stylohyoid, platySma), belly of digastic;
Nerves: CN VII (facial expression);

72

Abnormalities in 1st branchial arch development

Treacher collins syndrome (failure of 1st arch neural crest cells to migrate leading to mandibular hypoplasia, facial abnormalities)

73

Abnormalities in 2nd branchial arch development

Congenital pharyngo-cutaneous fistula: persistance of cleft and pouch leading to fistula between tonsillar area and lateral neck

74

Branchial arch derivatives of 3rd arch

Cartilage: greater horn of hyoid;
Muscles: Stylopharyngeus (think of stylopharyngeus innervated by the glossopharyngeal nerve);
Nerves: CN IX (stylo-pharyngeus), swallow stylishly

75

Branchial arch derivatives of 4th and 6th arch

Cartilage: thyroid, cricoid, arytenoids, corniculate, cuneiform;
Muscles: 4th-Most pharyngeal constrictors, cricothyroid, levator veli palatini, 6th- all intrinsic muscles of larynx except crycothyroid;
Nerves: 4th- CN X (superior laryngeal branch, simply swallow), 6th- CN X (recurrent laryngeal branch, speak)

76

Branchial arches 3 and 4 create what together

the posterior 1/3 of tongue

77

What is derived from this branchial pouch: 1st

Develops into the middle ear cavity, eustachian tube, mastoid air cells;
1st pouch contributes to endoderm-lined structures of ear

78

What is derived from this branchial pouch: 2nd

Develops into the epithelial lining of the palatine fossa

79

What is derived from this branchial pouch: 3rd

Dorsal wings-develops into the inferior parathyroids;
Ventral wings-develops into the thymus;
3rd pouch= 3 structures (thymus, left and right parathyroid);
3rd pouch ends up below the 4th

80

What is derived from this branchial pouch: 4th

Dorsal wings-develops into superior parathyroids

81

DiGeorge syndrome

Aberrant development of 3rd and 4th pouches leads to T cell deficiency (thymic aplasia) and hypocalcemia (failure of parathyroid development). Associated with cardiac defects (conotruncal anomalies)

82

MEN 2A

Mutation of Germline RET (neural crest cells);
Adrenal medulla (pheochromocytoma);
Parathyroid (tumor): 3rd and 4th pharyngeal pouch;
Parafollicular cells (medullary thyroid cancer): derived from neural crest cells: associated with 4th and 5th pharyngeal pouches

83

Cleft lip

Failure of fusion of the maxillary and medial nasal processes (formation of primary palate)

84

Cleft palate

Failure of fusion of the two lateral palatine processes or failure of fusion of lateral palatine processes with the nasal septum and/or median palatine process (formation of secondary palate)

85

Genital embryology: males and the SRY gene

SRY gene on chromosome Y produces testis determining factor (testes development)

86

Genital embryology: Male Sertoli cells make what

Secrete Mullerian inhibitory factor (MIF);
suppresses development of paramesonephric ducts

87

Genital embryology: Male leydig cells do what

Secrete androgens that stimulate development of mesonephric ducts

88

Mesonephric (wolffian) duct develops into

male internal structures (Except prostate): SEED;
Seminal vesicles;
Epididymis;
Ejaculatory Duct;
Ductus deferens

89

Bicornuate uterus

Results from incomplete fusion of the paramesonephric ducts (vs. complete failure of fusion, resulting in double uterus and vagina). Can lead to anatomic defects such as recurrent miscarriages

90

Lets say you have a male with SRY gene on his Y chromosome (normal), but he has no sertoli cells or no mullerian inhibitory factor

Develop both male and female internal genitalia and male external genitalia

91

What if you have a XY male that has a defect in 5alpha reductase

can't convert testosterone into dihydrotestosterone;
Male internal genitalia, ambiguous external genitalia until puberty (then increased testosterone will cause manly development)

92

What does this structure grow into when exposed to dihydrotestosterone (male) vs Estrogen (female): Genital tubercle

Men: glans penis, Women: Glans clitoris;
Men: Corpus cavernosum and spongiosum, women: vestibular bulbs

93

What does this structure grow into when exposed to dihydrotestosterone (male) vs Estrogen (female): urogential sinus

Men: bulbourethral glands of Cowper, Women: Greater vestibular glands of Bartholin;
Men: prostate gland, Women: Urethral and paraurethral glands of Skene

94

What does this structure grow into when exposed to dihydrotestosterone (male) vs Estrogen (female): Labioscrotal swelling

Men: scrotum, Women: Labia majora

95

Hypospadias

Abnormal opening of the urethra on inferior (ventral) side of penis due to failure of urethral folds to close;
More common than epispadius;
Fix to prevent UTIs and infertility;
Hypo is below

96

Epispadias

Abnormal opening of penile urethra on superior (dorsal) side of penis due to faulty positioning of genital tubercle;
Exstrophy of bladder is associated with epispadias;

97

What are the female and male remnants of: Gubernaculum

males: anchors testes within scrotum;
Females: ovarian ligament + round ligament of uterus.

98

What are the female and male remnants of: Processus vaginalis

Males: forms tunica vaginalis;
Female: obliterated

99

Venous drainage of gonads

Left ovary/testes drains into left gonadal vein into the left renal into the IVC;
Right ovary/testes drains into the right gonadal vein into the IVC

100

Lymphatic drainage of gonads

Ovaries/testes drain into the para-aortic lymph nodes;
Distal vagina/vulva/scrotum drain into the inguinal nodes;
Proximal vagina/uterus drains into the obturator, external iliac and hypogastric

101

Infundibulopelvic ligament (suspensory ligament of the ovaries): does what, contains what

Connects ovaries to lateral pelvic wall;
Contains the ovarian vessels;
Ligate vessels during oophorectomy to avoid bleeding;
Ureter courses retroperitoneally, close to gonadal vessels. At risk of injury during ligation of ovarian vessels

102

Cardinal ligament: does what, contains what

Connects cervix to side wall of pelvis;
contains uterine vessels;
Ureter at risk of injury during ligation of uterine vessels in histerectomy;

103

Round ligament of the uterus: does what

Uterine fundus to labia majora;
Derivative of gubernaculum. Travels through round inguinal canal; above the artery of sampson

104

Broad ligament: connects what, contains what

Connects uterus, fallopian tubes, and ovaries to pelvic side wall;
Ovaries, fallopian tubes, and round ligaments of uterus;
Mesosalpinx, mesometrium, and mesovarium are the components of the broad ligament

105

Ovarian ligament: connects what

Connects the medial pole of ovary to lateral uterus;
a derivative of the gubernaculum;
Ovarian Ligament Latches to Lateral uterus

106

Female epithelial histology that makes up the: vagina

Stratified squamous epithelium, nonkeratinized

107

Female epithelial histology that makes up the: Ectocervix

Stratified squamous epithelium, nonkeratinized

108

Female epithelial histology that makes up the: Endocervix

Simple columnar epithelium

109

Female epithelial histology that makes up the: Transformation zone

squamocolumnar junction (most common area for cervical cancer

110

Female epithelial histology that makes up the: Uterus

Simple columnar epithelium with long tubular glands

111

Female epithelial histology that makes up the: Fallopian tube

simple columnar epithelium, many ciliated cells, a few secretory (peg) cells

112

Female epithelial histology that makes up the: Ovary, outer surface

Simple cuboidal epithelium (germinal epithelium covering surface of ovary)

113

Female sexual response cycle

Most commonly describe as phase of excitement (uterus elevates, vaginal lubrication), plateau (expansion of inner vagina), orgasm (contraction of uterus), and resolution;
mediated by autonomic nervous system;
also causes tachycardia and skin flushing

114

Male reproductive anatomy: pathway of sperm during ejaculation

SEVEN UP;
Semininferous tubules, Epididymis, Vas deferens, Ejaculatory ducts, Nothing, Urethra, Penis

115

Autonomic innervation of the male sexual response

Erection is parasympathetic (via pelvic nerve);
NO leads to increased cGMP causing smooth muscle relaxation leading to vasodilation causing proerectile force;
NE leads to increased Calcium leading to smooth muscle contraction leading to vasoconstriction leading to antierectile force;
Emission is by sympathetic (via hypogastric nerve);
Ejaculation visceral and somatic nerves (pudendal nerve)

116

Seminiferous tubules: Spermatogonia (germ cells)

Maintain germ pool and produce primary spermatocytes;
They line the seminiferous tubules

117

Seminiferous tubules: sertoli cells

Secrete inhibit leading to inhibition of FSH;
Secrete androgen binding protein leading to maintenance of local levels of testosterone;
Tight junctions between sertoli cells form blood testis barrier helping to isolate gametes form autoimmune attacking;
Support and nourish developing spermatozoa;
regulate spermatogenesis;
Produce MIF;
Temperature sensitive: decrease sperm production, and decreased inhibin with increase in temperature;
Lines seminiferous tubules;
Converts testosterone and androstenedione to estrogen via aromatase

118

Seminiferous tubules: Leydig cells

Secrete testosterone in the presence of LH;
Testosterone production unaffected by temperature;
Located in interstitium;
Also contain aromatase

119

Estrogen: souce

Ovary (17beta-estradiol), Placenta (estriol), adipose tissue (estrone via aromatization);
Potency: estradiol > estrone > estriol

120

Estrogen: function

Development of genitalia and breast, female fat distribution;
Growth of follicle, endometrial proliferation, increased myometrial excitability;
upregulation of estrogen, LH, and progesterone receptors; feedback inhibition of FSH and LH, then LH surge; stimulation of prolaction secretion;
estrogen receptors in the cytoplasm, go to nucleus once bound

121

Progesterone

Source: Corpus leteum, placenta, adrenal cortex, testes;
Function: Stimulation of endometrial glandular secretion and spiral artery development;
Maintenance of pregnancy;
Decreases myometrial excitability;
Production of thick cervical mucus, which inhibits sperm entry into the uterus;
increases body temperature;
Inhibition of FSH and LH;
Uterine smooth muscle relaxation (preventing contractions);
Decreases estrogen receptor expressivity;
Prevents endometrial hyperplasia;
Fall in progesterone after delivery disinhibits prolactin leading to lactation;
Increased progesterone is indicative of ovulation
PRO-GESTerone is PRO-GESTation

122

Tanner stages of sexual development

Stage is assigned independently to genitalia, pubic hair, and breast;
1: Childhood (prepubertal);
2: Pubic hair appears (pubarche); breast buds form (thelarche);
3: Pubic hair darkens and becomes curly, penis size/length increases, breasts enlarge;
4: Penis width increases, darker scrotal skin, development of glans, raised areolae;
5: Adult, areolae are no longer raised

123

Menstrual cycle: Follicular and luteal phase length

Follicular can be variable;
luteal phase is always 14 days;
Ovulation to 14 days=menstruation (usually you count back 14 days from menstruation)

124

Menstrual cycle: What stimulates endometrial proliferation

estrogen

125

Menstrual cycle: what hormone maintains the endometrium to support implantation

Progesterone

126

Define oligomenorrhea

> 35 day cycle

127

Define polymenorrhea

128

Metrorrhagia

Intermenstrual bleeding;
Frequent but irregular menstruation;

129

Menorrhagia

Heavy menstrual bleeding;
>80 ml blood loss or >7 days menses

130

Menometrorrhagia

Heavy, irregular menstruation at irregular intervals

131

Oogenesis

Primary oocytes begin meiosis I during fetal life and complete meiosis I prior to ovulation;
Meiosis I is arrested in prOphase I for years until Ovulation (primary oocyte);
Meiosis II is arrested in metaphase II until fertilization (secondary oocytes);
If fertilization does not occur within 1 day, the secondary oocyte degenerates

132

Steps of ovulation

Increased estrogen, increased GnRH receptors on anterior pituitary. Estrogen then stimulates LH release (surge) leading to ovulation (rupture of follicle);
Increased temperature (progesterone induced)

133

Mittelschmerz

Refers to transient mid cycle ovulatory pain; classically associated with peritoneal irritation (e.g. follicular swelling/rupture, fallopian tube contraction);
Can mimic appendicitis

134

Where does fertilization commonly occur

Upper end of the fallopian tube (ampulla);
Occurs within first day of ovulation;

135

After fertilization of egg in ampulla, what happens

Implantation within the wall of the uterus occurs 6 days after fertilization;
Syncytiotrophoblasts secrete hCG, which is detectable 1 week after conception and on home test in urine 2 weeks after conception

136

Lactation after labor

After labor, the decreased progesterone and estrogen disinhibits lactation. Suckling is required to maintain milk production since increase nerve stimulation increases oxytocin and prolactin

137

Lactation: Prolactin's role

Induces and maintains lactation and decreased reproductive function

138

Lactation: Oxytocin's role

Assists in milk letdown;
promotes uterine contractions

139

Breast milk contains and has what benefits

Maternal immunoglobulins (mostly IgA);
Macrophages;
lymphocytes;
Still need to give vitamin D to baby;
Decreases child's chance of: asthma, allergies, diabetes, obesity;
decreases maternal risk of breast and ovarian cancer

140

hCG: source of it

Syncytiotrophoblasts of the placenta

141

hCG: function

Maintains the corpus luteum (and thus progesterone) for the 1st trimester (otherwise no luteal cell stimulation and abortion happens);
in the 2nd and 3rd trimester the placenta synthesizes its own estriol and progesterone and corpus luteum degenerates;
Used to detect pregnancy because it appears early in the urine;
alpha subunit of hCG is same as LH, FSH, and TSH so beta subunit is how it is distinguished;
hCG increased in multiple gestations and in pathologic states (e.g. hydatidiform mole, choriocarcinoma)

142

menopause

Decreased estrogen production due to age linked decline in number of ovarian follicles;
Average age of onset is 51 (earlier in smokers);
Usually preceded by 4-5 years of abnormal menstrual cycles;
source of estrogen (estrone) after menopause become peripheral conversion of androgens (increased androgens leads to hirsutism);
Massively increased FSH is specific for menopause (loss of estrogen's negative feedback), decreased Estrogen, increased LH, increased GnRH

143

Menopause causes HAVOCS

hot flashes;
Atrophy of vagina;
Osteoporosis;
Coronary artery disease;
Sleep disturbances

144

Spermatogenesis

Spermatogenesis begins at puberty with spermatogonia;
Full development takes 2 months;
Occurs in seminiferous tubules;
Produces spermatids that undergo spermiogenesis (loss of cytoplasmic contents, gain of acrosomal cap) to form mature spermatozoon;
Gonium is going to be sperm;
Zoon is Zooming to egg

145

Androgens: name them

Testosterone, Dihydrotestosterone (DHT), Androstenedione

146

Androgens: source

DHT and testosterone (testis, AnDrostenedione (ADrenal)

147

Androgens: potency

DHT > testosterone > androstenedione

148

Androgens: function of testosterone

Differentiation of epididymis, vas deferens, seminal vesicles (genitalia, except prostate);
Growth spurt: penis, seminal vesicles, sperm, muscle, RBCs;
Deepening of voice;
Closing of epiphyseal plates (via estrogen converted from testosterone);
libido

149

Androgens: Functions of DHT

Early- Differentiation of penis, scrotum, prostate;
Late-prostate growth, balding, sebaceous gland activity

150

How to convert testosterone to DHT

5 alpha reductase enzyme;

151

Androgens are converted to estrogens in males by

cytochrome p-450 aromatase (primarily in adipose tissue and the testis);

152

Exogenous testosterone

leads to inhibition of hypothalamic pituitary gonadal axis leading to decreased intratesticular testosterone leading to decreased testicular size and azoospermia (absence of motile sperm)

153

10-OH progesterone

Rises in the first semester like hCG, then falls off like hCG;
Made by the corpus luteum because placenta lacks 17 alpha hydroxylase;

154

Klinefelter Syndrome

XXY Male, 1:850;
See: testicular atrophy, eunuchoid body shape, tall, long extremities, gynecomastia, female hair distribution, may present with developmental delay;
Presence of Barr body (inactivated X chromosome);
Common cause of hypogonadism see in infertility workup;
Dysgenesis of seminiferous tubules leading to decreased inhibit and therefore increased FSH;
Abnormal leydig cell function leads to decreased testosterone causing increased LH and therefore increased estrogen

155

Turner syndrome

XO Female;
Short stature if untreated, ovarian dysgenesis (streak ovary), shield chest, bicuspid aortic valve, preductal coarctation (femoral

156

Double Y males

XYY, 1:1000;
Phenotypically normal;
very tall, severe acne, antisocial behavior (1-2%), Normal fertility, small percentage diagnosed with autism spectrum disorders

157

True hermaphroditism

46XX or 47 XXY, Very rare;
Also called ovotesticular disorder of sex development;
both ovary and testicular tissue are present (ovotestis);
ambiguous genitalia;

158

Trisomy 16

Never born, always die in utero;
most common genetic reason for death of fetus

159

Diagnosing disorders of sex hormones: increased LH and increased testosterone

Think defective androgen receptor

160

Diagnosing disorders of sex hormones: increased Testosterone and decreased LH

Testosterone secreting tumor, exogenous steroids

161

Diagnosing disorders of sex hormones: Decreased testosterone, increased LH

primary hypogonadism

162

Diagnosing disorders of sex hormones: Decreased testosterone, decreased LH

Hypogonadotropic hypogonadism

163

Female pseudohermaphrodite (XX)

Ovaries present but external genitalia are virilized or ambiguous;
Due to excessive and inappropriate exposure to androgenic steroids during early gestation (congenital adrenal hyperplasia or exogenous administration of androgens during pregnancy)

164

Male pseudohermaphrodite (XY)

Testes present, but external genitalia are female or ambiguous;
most common form is androgen insensitivity syndrome (testicular feminization)

165

Aromatase deficiency

inability to synthesize estrogens from androgens;
Masculinization of female (46,XX) infants (ambiguous genitalia);
increased serum testosterone and androstenedione;
can present with maternal virilization during pregnancy (fetal androgens cross the placenta)

166

Androgen insensitivity syndrome (46XY)

Defect in androgen receptor resulting in normal appearing female;
female external genitalia with rudimentary vagina;
uterus and fallopian tubes generally absent;
presents with scant sexual hair;
develops testes (often found in labia majora; surgically removed to prevent malignancy);
increased testosterone, estrogen, and LH (vs. sex chromosome disorders)

167

5alpha reductase deficiency

Autosomal recessive;
sex limited to genetic males (46XY);
inability to convert testosterone to DHT;
Ambiguous genitalia until puberty;
when increased testosterone causes masculinization/ increased growth of external genitalia;
testosterone/estrogen levels are normal;
LH is normal or increased;
internal genitalia are normal

168

Kallman syndrome

Failure to complete puberty;
a from of hypogonadotropic hypogonadism;
defective migration of GnRH cells and formation of olfactory bulb;
decreased synthesis of GnRH in the hypothalamus;
anosmia;
Decreased GnRH, FSH, LH, testosterone, and infertility (low sperm count or amenorrhea)

169

Hydatitdiform mole

Cystic swelling of chorionic villi and proliferation of chorionic epithelium (only trophoblast);
Treatment: dilation and curettage and methotrexate;
Monitor beta hCG

170

Complete Hydatidiform mole

Karyotype- 46,XX or 46,XY;
Massively increased hCG;
Increased uterine size;
2% convert to choriocarcinoma;
No fetal parts;
Enucleated egg + single sperm (subsequently duplicates paternal DNA), empty egg + 2 sperm is rare;
15-20% have complication of malignant trophoblastic disease (choriocarcinoma);
Symptoms- Vaginal bleeding, enlarged uterus, hyperemesis, pre-eclampsia, hyperthyroidism;
Imaging-honeycombed uterus or cluster of grates, snowstorm on ultrasound

171

Partial hydatidiform mole

Karyotype- 69,XXX or 69,XXY or 69,XYY;
increased hCG;
normal uterine size;
Rare for it to convert to choriocarcinoma;
Fetal parts are present (partial parts present);
Components- 2 sperm + 1 egg;
Low risk of malignancy (

172

Gestational HTN (pregnancy induced HTN)

BP > 140/90 mmHg after the 20th week of gestation;
no pre-existing HTN;
No proteinuria or end organ damage;
Treat: antihypertensives (alpha methyldopa, labetalol, hydralazine, nifedipine), deliver at 39 weeks;

173

Preeclampsia: presentation

Defined as HTN and proteinuria after 20th week of gestation to 6 weeks (160/100, with or without end organ damage, e.g. headache, scotoma, oliguria, increased AST/ALT, thrombocytopenia

174

Preeclampsia: Causes

Caused by abnormal placental spiral arteries, results in maternal endothelial dysfunction, vasoconstriction, or hyperreflexia

175

Preeclampsia: who is more likely to get it

Patients with preexisting: HTN, diabetes, chronic renal disease, or autoimmune disorders

176

Preeclampsia: Complications

Placental abruption, coagulopathy, renal failure, uteroplacental insufficiency, or eclampsia

177

Preeclampsia: treatment

Antihypertensives, deliver at 34 weeks if severe, 37 weeks if mild, IV magnesium sulfate to prevent seizure

178

Eclampsia

Preeclampsia + seizures in mom;
Maternal death due to stroke due to intracranial hemorrhage or ARDS;
Treat with antihypertensives, IV magnesium sulfate, immediate delivery

179

HELLP syndrome

Hemolysis, Elevated liver enzymes, Low Platelets;
A manifestation of severe preeclampsia, although may occur without HTN;
Treat by immediate delivery

180

Placental abruption (abruptio placentae)

Premature separation (separate or complete) of placenta form uterine wall before delivery of baby;
Risk factor: trauma, smoking, HTN, preeclampsia, cocaine abuse;
Presents as abrupt, painful bleeding (concealed or apparent) in 3rd trimester, Possible DIC, maternal shock, fetal distress;
Life threatening for mom and baby

181

Placenta accreta

Placenta attaches to myometrium without penetrating it, most common type;
Defective decidual layer leading to abnormal attachment and separation after delivery;
Risk factor: prior C section, inflammation, placenta previa
Presents as no separation of placenta after delivery of baby leading to massive bleeding, life threatening for mom

182

Placenta increta

Placenta penetrates into myometrium and attaches;
Defective decidual layer leading to abnormal attachment and separation after delivery;
Risk factor: prior C section, inflammation, placenta previa
Presents as no separation of placenta after delivery of baby leading to massive bleeding, life threatening for mom

183

Placenta Percreta

Placent penetrates (perforates) through the myometrium and into uterine serosa (invades entire uterine wall); can result in placental attachment to rectum or bladder;
Defective decidual layer leading to abnormal attachment and separation after delivery;
Risk factor: prior C section, inflammation, placenta previa
Presents as no separation of placenta after delivery of baby leading to massive bleeding, life threatening for mom

184

Pregnancy complications: Retained placental tissue

May cause postpartum hemorrhage;
increased risk of infection

185

Ectopic pregnancy

Most often in ampulla of fallopian tube;
suspect with Hx of amenorrhea, lower than expected hCG based on dates, and sudden lower abdominal pain, Hx of infertility, pelvic inflammatory disease;
confirm with ultrasound;
often mistaken as appendicitis;

186

Polyhydramnios

> 1.5 to 2 liters of amniotic fluid; Associated with fetal malformations (e.g. esophageal/duodenal atresia, anencephaly, both result in inability to swallow amniotic fluid), maternal diabetes, fetal anemia, multiple gestations

187

Oligohydramnios

188

Cervical pathology: dysplasia and carcinoma in situ

Disordered epithelial growth;
Begins at basal layer of squamocolumnar junction (transition zone) and extends outward;
Classified as CN I, 2, or 3 depending on extent of dysplasia;
associated with HPV 16 and 18 which produce both the E6 gene product (inhibits p53 suppressor gene) and E7 gene product (inhibits RB suppressor gene);
May slowly progress to invasive carcinoma if left untreated;
Typically asymptomatic (PAP smear detects it);
Can have vaginal bleeding (often post coital);
Risk factors- multiple sexual partners (#1), smoking, early sexual intercourse, HIV infection

189

Cervical pathology: invasive carcinoma

Often squamous cell carcinoma;
Pap smear can catch cervical dysplasia (koilocytes) before it progresses to invasive carcinoma;
lateral invasion can block ureters, causing renal failure

190

Endometritis

Inflammation of the endometrium (with plasma cells and lymphocytes);
associated with retained products of conception post delivery or foreign body such as an IUD;
Retained material promotes infection by bacterial flora from vagina or intestinal tract;
Treatment: gentamicin + clindamycin with or without ampicillin

191

Endometriosis: what is it?

Non-neoplastic endometrial glands/stroma outside of the endometrial cavity;
Can be found anywhere but most common in ovary, pelvis, and peirtoneum;
In ovary, appears as an endometrioma (chocolate cysts);
Can be due to retrograde flow, metastatic transformation of multipotent cells or transportation of endometrial tissue via lymphatic system

192

Endometriosis: Symptoms that bring patient into office

Characterized by cyclic pelvic pain, bleeding, dysmenorrhea, dyspareunia, dyschezia (pain with pooping), infertility;
normal sized uterus

193

Endometriosis: Treatment

Treatment- NSAIDs, OCPs, progesterone, GnRH agonists, surgery

194

Adenomyosis

Extension of endometrial tissue (glandular) into the uterine myometrium;
Caused by hyperplasia of the basalis layer of the enodmetrium;
Dysmenorrhea, menorrhagia;
Uniformly enlarged, soft, globular uterus;
Treatment is hysterectomy

195

Adenomyoma

polyp;
Well circumscribed collection of endometrial tissue within the uterine wall;
may contain smooth muscle cells;
Can extend into the endometrial cavity in the form of a polyp

196

Endometrial hyperplasia

abnormal endometrial gland proliferation usually caused by excess estrogen stimulation;
increased risk for endometrial carcinoma;
Clinically manifests as postmenopausal vaginal bleeding;
risk factors include anovulatory cycles, hormone replacement therapy, polycystic ovarian syndrome, and granulosa cell tumor

197

Endometrial carcinoma

Most common gynecologic malignancy;
peak occurrence at 55-65;
clinically presents as vaginal bleeding;
typically preceded by endometrial hyperplasia;
risk factors include prolonged use of estrogen without progestins, obesity, diabetes, HTN, nulliparity, and late menopause (any situation that raises estrogen);
Increased myometrial invasion leading to worse prognosis

198

Leiomyoma

fibroid;
Most common tumor in females;
Often presents as multiple discrete tumors;
increase incidence in blacks;
benign smooth muscle tumor;
malignant transformation rare;
Estrogen sensitive- tumor size will increase with pregnancy and decrease with menopause;
Peak occurrence is 20-40;
may be asymptomatic, cause bleeding or miscarriage;
does not progress to leiomyosarcoma!;
whorled pattern of smooth muscle with well-demarcated borders

199

Gynecologic tumor epidemiology: what is most common in US, what is most deadly

Incidence: endometrial > ovarian > cervical;
Worst prognosis: Ovarian > cervical > endometrial

200

Premature ovarian failure

Premature atresia of ovarian follicles in women of reproductive age;
Patients present with signs of menopause after puberty but before age 40;
Decreased estrogen, increased LH and FSH

201

Most common causes of anovulation

Pregnancy, polycystic ovarian syndrome, obesity, HPO axis abnormalities, premature ovarian failure, hyperprolactinemia, thyroid disorders, eating disorders, female athletes, Cushing syndrome, adrenal insufficiency

202

Polycystic Ovarian Syndrome: physiology

Hyperandrogenism due to deranged steroid synthesis by theca cells, hyperinsulinemia;
Estrogen increases steroid hormone-binding globulin and decreases LH, leading to decreased free testosterone;
Insulin and testosterone decrease SHBG leading to increased free testosterone;
Increased LH due to pituitary/hypothalamus dysfunction;
Results in enlarged, bilateral cystic ovaries;

203

Polycystic Ovarian Syndrome: presentation

Presents with amenorrhea/oligomenorrhea, hirsutism, acne, infertility;

204

Polycystic Ovarian Syndrome: Associated with

Associated with obesity;
Increased risk of endometrial cancer secondary to increased estrogens from aromatization of testosterone and absence of progesterone;

205

Polycystic Ovarian Syndrome: treatment for Hirsutism, acne:

weight reduction, OCPs (estrogen increases SHBG and decreased LH leading to decreased free testosterone), antiandrogens;

206

Polycystic Ovarian Syndrome: treatment for infertility:

clomiphene citrate (block negative feedback of estrogen, decreased FSH and LH), metformin (increases insulin sensitivity, decreases insulin levels, results in decreased testosterone, enables LH surge);

207

Polycystic Ovarian Syndrome: treatment for endometrial protection:

Cyclic progesterone (antagonizes endometrial proliferation)

208

Follicular ovarian cyst

distention of unruptured graafian follicle;
may be associated with hyperestrogenism and endometrial hyperplasia;
Most common ovarian mass in young women

209

Ovarian cyst: Corpus Leteum cyst

Hemorrhage into persistent corpus luteum;
commonly regresses spontaneously

210

Ovarian cyst: Theca-lutein cysts

Often bilateral/multiple;
Due to gonadotropin stimulation;
Associated with choriocarcinoma and moles;

211

Ovarian cyst: hemorrhagic cysts

blood vessel rupture in cyst wall;
cyst grows with increased blood retention;
Usually self-resolves

212

Ovarian cysts: Dermoid cyst

Mature teratoma;
Cystic growths filled with various types of tissue such as fat, hair, teeth, bits of bone, and cartilage

213

Ovarian cysts: Endometrioid cysts

Endometriosis within ovary with cyst formation;
varies with menstrual cycle;
when filled with dark, reddish-brown blood it is called a "chocolate cyst"

214

Serous cystadenoma

most common benign ovarian neoplasm;
thin walled, uni or multilocular;
lined with fallopian like epithelium;
often bilateral

215

Mucinous Cystadenoma

benign ovarian neoplasm;
Multiloculated;
large;
Lined by mucus secreting epithelium

216

Endometrioma

benign ovarian neoplasm;
Mass arising from from growth of ectopic endometrial tissue;
Complex mass on ultrasound;
presents with pelvic pain, dysmenorrhea, dyspareunia

217

Mature cystic teratoma (dermoid cyst)

benign ovarian Germ cell tumor;
most common ovarian tumor in 20-30 year olds;
can contain elements from all 3 germ layers (teeth, hair, sebum are common);
Can present as pain due to secondary ovarian enlargement or torsion;
Can also contain functional thyroid tissue and present as hyperthyroidism (struma ovarii)

218

Brenner tumor

benign ovarian neoplasm;
Looks like bladder;
Solid tumor that is pale yellow-tan in color and appears encapsulated;
"coffee bean" nuclei on H&E stain

219

Fibromas of ovary

benign ovarian neoplasm;
bundles of spindle shaped fibroblasts;
Meigs Syndrome-triad of ovarian fibroma, ascites, and hydrothorax;
pulling sensation in groin

220

Thecoma in ovary

benign ovarian neoplasm;
Like granulosa cell tumors, may produce estrogen;
usually present as abnormal uterine bleeding in a postmenopausal woman.

221

Immature teratoma

Malignant ovarian neoplasm;
aggressive, contains fetal tissue, neuroectoderm;
typically has immature/embryonic like neural tissue (mature teratoma more likely to contain thyroid tissue)

222

Serous cystadenocarcinoma

most common malignant ovarian neoplasm;
frequently bilateral;
Psammoma bodies;

223

Mucinous cystadenocarcinoma

Malignant ovarian neoplasm;
Pseudomyxoma peritonei- intraperitoneal accumulation of musinous material from ovarian or appendiceal tumor

224

Dysgerminoma

Malignant ovarian neoplasm;
Most common in adolescents;
equivalent to male seminoma but rarer;
1% of all ovarian tumors;
30% of all germ cell tumors;
sheet of uniform "fried egg" cells;
hCG, LDH=tumor markers

225

Choriocarcinoma

Rare Malignant ovarian neoplasm;
Can develop after pregnancy in mother or baby;
malignancy of trophoblastic tissue (crytotrophoblasts, syncytiotrophoblasts);
no chorionic villi present;
increased frequency of theca-lutein cysts;
Presents with abnormal beta-hCG, SOB, hemoptysis;
Hematogenous spread to lungs;
very responsive to chemo

226

Yolk sac (endodermal sinus) tumor

Aggressive Malignant ovarian neoplasm;
in ovaries or testes and sacrococcygeal area in young children;
most common tumor in male infanats;
yellow, friable (hemorrhagic), solid mass;
50% have Schiller-Duval bodies (resemble glomeruli;
AFP=tumor marker

227

Krunkenberg tumor

GI malignancy that metastasizes to the ovaries, causing a mucin secreting signet cell adenocarcinoma

228

Vaginal tumor: squamous cell carcinoma

Usually secondary to cervical clear cell carcinoma;
primary vaginal carcinoma rare

229

Vaginal tumor: Clear cell adenocarcinoma

Affects women who had exposure to DES in utero

230

Vaginal tumor: sarcoma botryoides (rhabdomyosarcoma variant)

Affects girls

231

Breast tumor: Fibroadenoma

Benign tumor;
Small, mobile, firm mass with sharp edges;
most common tumor in those

232

Breast tumor: Intraductal papilloma

Benign tumor;
Small tumor that grows in lactiferous ducts;
Typically beneath areola;
Serous or bloody nipple discharge;
Slight (1.5-2x) increase in risk for carcinoma

233

Breast tumor: Phyllodes tumor

Benign tumor;
Large bulky mass of connective tissue and cysts. Leaf-like projections;
Most common in 6th decade;
Some may become malignant

234

Overview of malignant breast tumors

Commonly postmenopausal;
usually arise from terminal duct lobular unit;
overexpression of estrogen/progesterone receptors or c-erbB2 (HER-2, an EGF receptor) is common;
Triple negative (ER-, PR-, and Her2/Neu-) more aggressive;
type affects therapy and prognosis;
Axillary lymph node involvement indicating metastasis is the single most important prognostic factor;
Most often located in upper-outer quadrant of breast;

235

Risk factors for malignant breast tumors

increased estrogen exposure;
Increase total number of menstrual cycles;
older age at 1st live birth;
obesity (increased estrogen exposure as adipose tissue has aromatase to convert androstenedione to estrone);
BRCA1 and BRCA2 gene mutations;
African American ethnicity (increases risk for triple negative breast cancer)

236

Breast tumor: Ductal carcinoma in situ

noninvasive;
Fills ductal lumen;
arises from ductal atypia;
Often seen early as microcalcification on mammography;
Early malignancy without basement membrane penetration

237

Breast tumor: Comedocarcinoma

noninvasive;
Ductal, caseous necrosis;
Subtype of DCIS

238

Breast tumor: paget disease

noninvasive;
Results from underlying DCIS;
exzematous patches on nipple;
paget cell=large cells in epidermis with clear halo;
Nipple inflammation, pigmentation;
PAS + (stains carbohydrate macromolecules like mucin);
Burning and itching of breast;
Suggests underlying DCIS;
also seen in vulva, though does not suggest underlying malignancy

239

Breast tumor: Invasive ductal

Invasive;
firm, fibrous, "rock-hard" mass with sharp margins and small, glandular, duct like cells;
Grossly, see classic "stellate" infiltration;
Worst and most invasive;
most common (76%) breast cancer

240

Breast tumor: Invasive lobular

Invasive;
Orderly row of cells (indian file);
often bilateral with multiple lesions in the same location

241

Breast tumor: Medullary

Invasive;
Fleshy, cellular lymphocytic infiltrate;
Good prognosis

242

Breast tumor: inflammatory

Invasive;
Dermal lymphatic invasion by breast carcinoma;
Peau d'orange (breast skin looks like orange peel);
neoplastic cells block lymphatic drainage;
50% survival at 5 years

243

Mullerian inhibitory factor: what does it do in development

In men, in utero, mullerian inhibitory factor is a requirement to block the development of female structures (if missing you can get a normal external fertile adult dude, but inside he will have a uterus)

244

mixed testicular tumor

Shows differentiation consistent with multiple types of tumors

245

Proliferative breast disease: overview and types

Most common cause of breast lumps from age 25 to menopause;
presents with pre-menstrual breast pain and multiple lesions, often bilateral;
Fluctuation in size and mass;
Usually does not indicate an increase risk of carcinoma;
4 types are Fibrosis, Cystic, Sclerosing adenosis, Epithelial hyperplasia

246

Proliferative breast disease: fibrosis type

Hyperplasia of breast stroma

247

Proliferative breast disease: Sclerosing adenosis

Increased acini and intralobular fibrosis;
Associated with calcifications;
Often confused with cancer;
Increased risk (1.5-2x) of cancer

248

Proliferative breast disease: Cystic type

Fluid filled, blue dome;
Ductal dilation

249

Proliferative breast disease: Epithelial hyperplasia

Increased number of epithelial cell layers in terminal duct lobule. Increased risk of carcinoma with atypical cells;
Occurs in women>30 years old

250

Acute mastitis

Breast abscess;
during breast feeding, increased risk of bacterial infection through cracks in the nipple;
S. auereus is the most common pathogen;
Treat with dicloxacillin and continued breast-feeding

251

Fat necrosis of breast

A benign, usually painless lump;
forms as a result of breast trauma;
abnormal calcifications on mammography;
biopsy shows necrotic fat, giant cells;
Up to 50% of patients may not report trauma

252

Gynecomastia

Occurs in males;
results from hyperestrogenism (cirrhosis, testicular tumor, puberty, old age), klinefelter syndrome, or drugs (spironolactone, Dope (marijuana), Digitalis, Estrogen, Cimetidine, Alcohol, Heroin, Dopamine D2 antagonists, Ketoconazole, Some Dope Drugs Easily Create Awkward Hairy DD Knockers)

253

Benign prostatic hyperplasia

Common in men >50;
Hyperplasia (not hypertrophy);
characterized by a smooth elastic, firm nodular enlargement of the periurethral lobes which compress the urethra into a vertical slit;
Not pre-malignant;
Will increase PSA;
Treatment: alpha1 antagonists (terazosin, tamsulosin), which cause relaxation of smooth muscle, Finasteride

254

Prostatic adenocarcinoma

Common in men >50;
arises most often from the posterior lobe (peripheral zone) of the prostate gland;
Increased PSA followed by needle core biopsy;
Prostatic acid phosphatase (PAP) and PSA are useful tumor markers (increased total PSA with decreased fraction of free PSA);
Obsteoblastic metastases in bone may develop in late stages, as indicated by lower back pain and an increase in serum ALP and PSA

255

Cryptorchidism

Undescended testis (one or both);
impaired spermatogenesis (since sperm develop best at temperatures

256

Varicocele

Dilated veins in pampiniform plexus as a result of increased venous pressure;
most common cause of scrotal enlargement in adult males;
most often on the left side (left vein drains into left renal vein);
Can cause infertility due to increased temperature;
Bag of worms appearance;
Diagnosed by ultrasound Doppler;
Treatment- Varicocelectomy, embolization by interventional radiology

257

Testicular germ cell tumors: overview

95% of all testicular tumors;
most often occur in young men;
risk factor: cryptorchidism, Klinefelter syndrome;
Can present as a mixed germ cell tumor;
Differential diagnosis for testicular mass that does not transilluminated is cancer

258

Testicular germ cell tumors: Seminoma

Malignant;
Painless, homogenous testicular enlargement;
most common testicular tumor, most common in 3rd decade, never in infancy;
Large cells in lobules with watery cytoplasm and a fried egg appearance;
Increased placental AL;
Radiosensitive;
Late metastasis, excellent prognosis

259

Testicular germ cell tumors: Yolk sac (endodermal sinus) tumor

Yellow, mucinous;
aggressive malignancy of testes, analogous to ovarian yolk sac tumor;
Schiller Duval bodies resemble primitive glomeruli;
Most common testicular tumor in boys

260

Testicular germ cell tumors: Choriocarcinoma

Malignant;
Increase in hCG;
Disordered syncytiotrophoblastic and Cytotrophoblastic elements;
Hematogenous metastases to lungs and brain (may present with hemorrhagic stroke due to bleeding into the metastasis. may produce gynecomastia or symptoms of hyperthyroidism (hCG is an LH and TSH analog)

261

Testicular germ cell tumors: Teratoma

Unlike in females, mature teratoma in adult males may be malignant;
benign in children;
increased hCG and/or AFP in 50% of cases

262

Testicular germ cell tumors: Embryonal carcinoma

malignant, hemorrhagic mass with necrosis;
painful;
worse prognosis than seminoma;
Often glandular/papillary morphology;
"Pure" embryonal carcinoma is rare, most commonly present as mixed tumor;
When "Pure" may present with increased hCG and normal AFP

263

Testicular non-germ cell tumors: Leydig cell

Contains Reinke crystals;
usually androgen producing, gynecomastia in men, precocious puberty in boys;
Golden brown color

264

Testicular non-germ cell tumors: Sertoli cell

Androblastoma from sex cord stroma

265

Testicular non-germ cell tumors: Testicular lymphoma

Most common testicular cancer in older men;
not a primary cancer, arises form lymphoma metastases to testes;
Aggressive

266

Tunica Vaginalis Lesions

Lesions in the serous covering of testis present as testicular masses that can be transluminated (vs. testicular tumors);
Hydrocele-increased fluid secondary to incomplete obliteration of processus vaginalis;
Spermatocele-Dilated epididymal duct

267

Penile Pathology-Squamous cell carcinoma

Most common in Asia, Africa, and South America;
Precursor in situ lesions- Bowen disease (in penile shaft, presents as leukoplakia), erythroplasia of Queyrat (cancer of glans, presents as erythroplakia), Bowenoid papulosis (presents as reddish papules);
Associated with HPV and lack of circumcision

268

Penile pathology- Priapism

Painful sustained erection not associated with sexual stimulation or desire;
Associated with trauma, sickle cell disease, medications (anticoagulants, PDE-5 inhibitors, antidepressants, alpha blockers, cocaine)

269

Leuprolide

GnRH analog with agonist properties when used in pulsatile fashion, antagonist when used continuously (down-regulates GnRH receptors in anterior pituitary);
Used for: infertility (pulsatile), prostate cancer (continuous), uterine fibroids (continuous), Precocious puberty (continuous);
Toxicity: antiandrogen, nausea, vomiting

270

Estrogen Agonists

Ethinyl estradiol, DES, Mestranol;
Estrogen receptor agonists;
Used for hypogonadism or ovarian failure, menstrual abnormalities, HRT in postmenopausal women, used men for androgen-dependent prostate cancer;
Toxicity is increased risk of endometrial cancer, bleeding in postmenopausal women, clear cell adenocarcinoma of vagina in females exposed to DES in utero, increased risk of thrombi;
Contraindications would be ER + breast cancer, history of DVTs

271

Clomiphene

Selective Estrogen Receptor Modulators (SERMs);
Antagonist at estrogen receptor in hypothalamus, prevents normal feedback inhibition and increased release of LH and FSH from pituitary, which stimulates ovulation;
Used to treat infertility due to anovulation (e.g. PCOS);
May cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual disturbances

272

Tamoxifen

Selective Estrogen Receptor Modulators (SERMs);
Antagonist at breast, agonist at uterus and bone;
Associated with endometrial cancer, thromboembolic events;
Primarily used to treat and prevent recurrence of ER + breast cancer

273

Raloxifene

Agonist on bone;
Antagonist at uterus;
also increase risk of thromboembolic events and decreased resorption of bone so it is used in osteoporosis

274

Hormone replacement therapy

Used for relief or prevention of menopausal symptoms (e.g. hot flashes, vaginal atrophy) and osteoporosis (increased estrogen, decreased osteoclast activity);
Unopposed estrogen replacement therapy increases the risk of endometrial cancer, so progesterone is added;
possible increased cardiovascular risk

275

Anastrozole and exemestane

aromatase inhibitors used in postmenopausal women with breast cancer

276

Progestins

Mechanism: bind progesterone receptors, decreased growth and increased vascularization of endometrium;
Used for oral contraceptives and in the treatment of endometrial cancer and abnormal uterine bleeding

277

Mifepristone (RU-486)

Mechanism: Competitive inhibitor of progestins at progesterone receptors;
Used for termination of pregnancy, administered with misoprostol (PGE1);
Toxicity is heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain

278

Oral contraceptin

Estrogen and progestins inhibit FSH/LH and thus prevent estrogen surge;
No estrogen surge then no LH surge then no ovulation;
Progestins cause thickening of the cervical mucus, thereby limiting access of sperm to uterus;
Progestins also inhibit endometrial proliferation, thus making endometrium less suitable for the implantation of an embryo;
Contraindications- smokers>35 years old, patients with Hx of thromboembolism and stroke or history of estrogen-dependent tumor

279

Terbutaline

Beta 2 agonist that relaxes the uterus;
used to decrease contraction frequency in women in labor

280

Danazol

Mechanism: synthetic androgen that acts as partial agonist at androgen receptors;
Used for- endometriosis and hereditary angioedema;
Toxicity- weight gain, edema, acne, hirsutism, masculinization, decreased HDL levels, hepatotoxicity

281

Testosterone, methyltestosterone

Mechanism: agonist at androgen receptor;
used for-treats hypogonadism and promotes development of secondary sex characteristics, stimulation of anabolism to promote recovery after burn or injury;
Toxicities are masculinization of females, decreased intratesticular testosterone in males by inhibiting LH via negative feedback leading to gonadal atrophy, Premature closure of epiphyseal plates, Increased LDL and decreased HDL

282

Finasteride

A 5 alpha reductase inhibitor (decreased testosterone to DHT);
Useful in BPH;
Also promotes hair growth-used to treat male pattern baldness;

283

Flutamide

A non-steroidal competitive inhibitor of androgens at testosterone receptor;
used in prostate carcinoma

284

Ketoconazole

Inhibits steroid synthesis (inhibits 17,20 desmolase);
used in the treatment of PCOS to prevent hirsutism;
side effects of gynecomastia and amenorrhea

285

Sprionolactone

Inhibits steroid binding, inhibits 17alpha hydroxylase, inhibits 17,20 desmolase
used in the treatment of PCOS to prevent hirsutism;
side effects of gynecomastia and amenorrhea

286

Tamsulosin

alpha1 antagonist used to treat BPH by inhibiting smooth muscle contraction;
selective for alpha1A,D receptors found on prostate vs vascular alpha1B receptors

287

Sildenafil, vardenafil, tadalafil

Mechanism-inhibit phosphodiesterase 5, causing increased cGMP, smooth muscle relaxation in the corpus cavernosum, increased blood flow, and penile erection;
Uses: treatment of erectile dysfunction;
Toxicity- headache, flushing, dyspepsia, impaired blue-green color vision. Risk of Life threatening hypotension in patients taking nitrates