Monster Sdr Flashcards Georgetown Smp

Front 1

What is the most common cause of abdominal mass in an infant? What should you think if you are examining an infant with a mass?

Back 1

Multicystic Dysplastic Kidney!!

eww

Hint 1

Front 2

What something most people don't usually find until they start drinking a lot of beer (and making a lot of pee) in college?

Back 2

Antenatal Hydronephrosis:
UPJ Obstruction

urine cant get through that UPJ obstruction... causes pressure in the kidneys... causes pain

Hint 2

pressure in the kidney will turn in to lower GFR rate--> higher creatinine levels in the body

Front 3

Back 3

Hint 3

Lymphatic vessels from deep parts of the perineum accompany the internal pudendal blood vessels and drain mainly into internal iliac nodes in the pelvis.
Lymphatic channels from superficial tissues of the penis or the clitoris accompany the superficial external pudendal blood vessels and drain mainly into superficial inguinal nodes, as do lymphatic channels from the scrotum or labia majora (Fig. 5.79). The glans penis, the glans clitoris, labia minora, and the terminal inferior end of the vagina drain into deep inguinal nodes and external iliac nodes.
Lymphatics from the testes drain via channels that ascend in the spermatic cord, pass through the inguinal canal, and course up the posterior abdominal wall to connect directly with lateral aortic or lumbar nodes and pre-aortic nodes around the aorta, at approximately vertebral levels LI and LII. Therefore disease from the testes tracks superiorly to nodes high in the posterior abdominal wall and not to inguinal or iliac nodes.

Front 4

WTF is going on here? How can we tell what the lower pole(s) of the kidney are?

Back 4

Bilateral Ureteral Reflux

L incomplete duplication
R complete duplication
Drooping lily sign

Hint 4

Front 5

What happens if you have a mom come in complaining her daughter is having a lot of trouble with potty training and she is still wearing diapers after several years? What type of malformation could she have?

Back 5

Ectopic ureter

Can empty anywhere into Wolfian (mesonephric) duct
Prostate, seminal vesical, posterior urethra
Epoophoron, Gartner’s duct, vagina, cervix
Can cause obstruction of kidney, UTI
Incontinence in girls

Hint 5

Front 6

WTF is the Weigert Meyer law? What does it have to do with duplication?

Back 6

Weigert Meyer law
Lower pole ureter empties into the bladder superiorly and laterally
Associated with reflux

Upper pole ureter empties into the bladder inferiorly and medially
Associated with obstruction

Hint 6

Front 7

What is the difference between the labia minora and majora?

Back 7

Majora has more sebaceous glands, hair follicoles, etc

Front 8

Describe the 4 different histological layers of the ovary?

Back 8

(1) the outermost is a single layer of cuboidal “germinal” epithelial cells. It’s kind of a misnomer, since
these cells aren’t germinal, so don’t be fooled! Remember that the majority of ovarian cancers occur in
these cells,
(2) a thin layer called the tunica albuginea which is mostly just connective tissue,
(3) a thick cortex, which contains the oocytes, and
(4) the medulla, comprised of connective tissues and blood vessels.

Hint 8

. General Features
a. Functions in gamete production (exocrine) and sex hormone production (endocrine).
b. Anatomical Structure - Almond shaped body 3cm long x 1.5 cm wide x 1 cm thick (Fig. 3). Outer layer consists of a simple squamous/cuboidal/columnar germinal epithelium (misnomer) underlayed by the tunica albuginea (dense connective tissue). Beneath the tunica albuginea occurs the cortex containing the ovarian follicles in various stages of development. The medulla (Fig. 3) occupies the central region of the ovary and consists of blood vessels and connective tissue.

Front 9

Name the (8) different stages of follicular development. What is special about each stage? What causes them to change? WHEN IS THE OOCYTE ARRESTED IN METAPHASE I?

Back 9

1. Primordial Follicles
2. Primary Unilaminar Follicles
3. Primary Multilaminar Follicles
4. Secondary Follicles
5. Tertiary (Graffian) Follicles
6. Corpus Luteum
7. Corpus Albicans
8. Atretic Follicles

Hint 9

Ovarian Follicular Development
1. PRIMORDIAL FOLLICLES - present before birth, consist of a primary oocyte arrested in (dictyotene) MEIOTIC PROPHASE I surrounded by a layer of flattened follicular cells. Outside of follicular cells occur stromal cells. Primordial follicles have not yet responded to FSH. At puberty cyclic secretion of FSH stimulates groups of follicles to undergo development and produce estrogen. Every 28 days up to 20 primordial follicles respond to FSH. Their follicular cells acquire more FSH receptors and become more columnar (now called GRANULOSA cells).
2. PRIMARY UNILAMINAR FOLLICLES - consists of a PRIMARY OOCYTE surrounded by one (unilaminar) or layer of GRANULOSA CELLS.
3. PRIMARY MULTILAMINAR FOLLICLES - consists of a PRIMARY OOCYTE surrounded by more than one (MULTILAMINAR) layers of GRANULOSA CELLS. The granulosa cells and the oocyte together deposit an extracellular coat (ZONA PELLUCIDA) onto the primary oocyte. The zona pellucida is traversed by delicate cytoplasmic processes from the granulosa cells (FILOPODIA) and MICROVILLI projecting from the oocyte. The granulosa cells continue to divide forming a multilaminar layer surrounding the oocyte. Concurrently, the stromal cells differentiate to form the THECA INTERNA.
4. SECONDARY FOLLICLES - identified by the presence of an ANTRUM (cavity) formed from accumulations of hyaluronic acid-rich fluid (FOLLICULAR LIQUOR). Around time of transition from primary multilaminar to secondary follicle the first meiotic division is completed to produce an oocyte in the SECOND MEIOTIC PROPHASE. The follicular liquor contains oocyte meiosis inhibitor (OMI) that maintains arrest of the oocyte in MEIOTIC PROPHASE II (dictyate stage). The theca further differentiates into a THECA INTERNA and a THECA EXTERNA. The theca interna cells are steroidogenic producing ANDROSTENEDIONE. This intermediary of steroidogenesis passes into the follicle proper and is metabolized by THE GRANULOSA CELLS into ESTROGEN. The theca externa cells consist mainly of connective tissue.
5. GRAFFIAN (TERTIARY) FOLLICLE – is the dominant follicle larger than all other less well developed follicles. It contains a very large antrum filled with liquor folliculi. The oocyte is eccentrically located and connected to a layer of granulosa cells that line the inner aspect of the mature follicle by a PEDICLE of granulosa cells. The inner most single layer of granulosa cells surrounding the oocyte is termed the CORONA RADIATA. Outside of the corona radiata are several more accumulations of granulosa cells continuous with the pedicle termed the CUMULUS OOPHORUS. As the dominant follicle bulges from the surface of the ovary a LH surge brings about final maturation of the follicle. The rising titer of LH overrides the action of OMI resulting in resumption of meiosis with the OOCTYE ARRESTED IN METAPHASE II. Concurrently, the follicle ruptures dispersing OMI and ovulation occurs. Ovulation is thought to occur as a function of enzymatic dissolution of the connective tissue rather than an increase in pressure. The ovulated oocyte remains in metaphase II and only can be completed if fertilization takes place. The corona radiata (granulosa cells) remain attached to the ovum following ovulation even following fertilization. The zona pellucida surrounding the oocyte.
6. CORPUS LUTEUM (yellow body) - formed after ovulation from the remnants of the ruptured graffian follicle. After ovulation the follicular fluid is lost resulting in the collapse of the follicular wall forming a pleated corpus luteum (Fig. 5). The granulosa cells and the theca interna that remain in the ovary form a TEMPORARY ENDOCRINE GLAND whereby elevated progesterone and estrogen prevent development of any new follicles and prevent ovulation for the remainder of that cycle. This is the basis of the contraceptive pill. Under the influence of LH from the anterior pituitary the granulosa cells of the former graffian follicle (converted androstenedione to estrogen) become enlarged, occupy most of the space of the corpus luteum, and form the GRANULOSA LUTEIN CELLS that now secrete PROGESTERONE. The former theca interna of the graffian follicle (secreted androstenedione) become small darkly staining cells called the THECA LUTEIN (PARALUTEIN) CELLS that now produce ESTROGEN. If pregnancy does not occur in the following two weeks progesterone from the granulosa lutein cells negatively feeds back to the pituitary reducing LH secretion, causing degeneration of the corpus luteum into A CORPUS ALBICANS. If pregnancy occurs the corpus luteum is rescued from degeneration by chorionic gonadotrophin (hCG) produced by the placenta, which is homologous to LH.
7. CORPUS ALBICANS - if pregnancy does not occur the corpus luteum, deprived of LH, degenerates by autolysis and phagocytosis by macrophages. The residual scar of connective tissue that results from the absorptive process may take years to completely disappear.
8. ATRETIC FOLLICLES - most follicles do not fully develop into mature follicles. Many partially developed follicles become developmentally arrested and degenerate, characterized by detachment of granulosa cells, death of the oocyte and formation of pycnotic (dark) bodies (APOPTOSIS). Follicular atresia occurs from the time of birth until menopause. However it is most prominent just after birth and during pregnancy.

Front 10

Which cartoon character does this most resemble and why?

Back 10

Which part matches what?

Hint 10

Penis
a. The penis consists of the urethra and three parallel cavernous bodies. Two of these, the paired corpus cavernosa lie dorsally. The corpus spongiosum (also called corpus cavernosa urethrae) surrounds the urethra, begins at the base of the penis as an expanded bulbous portion and terminates as the glans penis.
b. A dense fibroelastic connective tissue layer, the tunica albuginea surrounds the corpus cavernosa. This forms a septum in the midline that is incomplete in the distal region to allow equilibration of blood flow between the two corpora cavernosa. The connective tissue layer around the corpus spongiosum is thinner with more elastic fibers that allow the urethra to remain patent during ejaculation.

Penis Clinical Relevance
a. Impotence is an inability to achieve erection. This may be a manifestation of neurological or emotional dysfunction or in other circumstances may be caused by congenital circulatory disorders of the penis.
b. Infections of the penis include the various venereal diseases.

Urethra
a. The urethra extends from the bladder to the external meatus on the glans penis. It is divided into 3 parts: (1) prostatic, (2) membranous, and (3) penile. The prostatic urethra is lined by a transitional epithelium. The membranous and penile urethra can be either stratified or pseudostratified columnar epithelium. Urethral glands occur in the submucosal connective tissue.
b. Infections of the urethra (E. coli) if not treated can retrograde infect the bladder, seminal vesicles, and epididymis.

Front 11

What is important to remember about the seminal vesicles?

Back 11

THERE IS NO SPERM IN IT!! (a misnomer!-- dont F*ck that up

Front 12

Whats the difference between corpora amylacae and copra erinase?

Back 12

The prostate has structures called corpora amelase, which are concentric concretions. This is a
distinguished histological feature of the prostate gland.

Front 13

What stage is this PRIMARY FOLLICLE in?

Back 13

Miotic prophase I

Hint 13

Front 14

What is the most common type of anesthetic block during baby delivery? Where would you aim for it?

Back 14

Blocking the pudendal nerve with injection of local anesthetic is used for vaginal deliveries and for minor surgeries of the vagina and perineum.
The injection is made where the pudendal nerve crosses behind the ischial spine.
Block can be done through the vagina (transvaginal) or through the overlying skin (perineal - transcutaneous).
The vaginal approach is more reliable and is used most often, except when an engaged head makes vaginal palpation more difficult.

Hint 14

Front 15

How can you tell the difference between a male and a female pelvis?

Back 15

Hint 15

more fun facts!

Front 16

What is the function of this area? What happens if it is messed up?

Back 16

Hint 16

Front 17

What is the nerve supply to these muscles? (we are looking at it from below)

Back 17

Front 18

Which muscles constrict during female orgasm? (tehehe...)

Back 18

Pelvic floor muscles! (supplied by the pudendal nerve)

Hint 18

Front 19

The perineum is _______ the pelvic diaphram

Back 19

BELOW!! DONT F*CKING FORGET IT

Front 20

Which muscle help prevent you from pooping your pants?

Back 20

Front 21

Describe all that encompasses the perineum?

Back 21

Front 22

Which anatomical muscle provides "supple" support for the penis/ clitoris?

Back 22

Front 23

Which structures come together to form the penis / clitoris ?

Back 23

Front 24

Go through the THREE LAYERS!!

Back 24

Hint 24

Front 25

Where are the bulbourethral glands located?

Back 25

Hint 25

This is a cornal image of the pubic arches

Front 26

What horrible things can happen if the perineal body tears during childbirth? What sorts of procedures could we do to avoid this?

Back 26

Hint 26

Episiotomy:

Benefits
+Speeds up the birth.
+Prevents tearing.
+Protects against incontinence.
+Heals easier than tears.

Dangers
-Infection.
-Increased pain.
-Longer healing times.
-Increased discomfort when intercourse is resumed.

Front 27

Which area is the prostate? Pelvic bone? Crura? Bulb?

Back 27

(urogential diaphram is in between the two pubic bones)

Front 28

The urogenital diaphragm (sphincter urethra muscle) suspends the roots of the penis and clitoris from it. The latter lie below the UG diaphragm.
The perineal region is composed of 2 pouches, the superficial perineal pouch and the deep perineal pouch.


What are the contents of the superficial/ deep pouches in the male/ female?

Back 28

Hint 28

Front 29

What is "The mother artery of the pelvis"?

Back 29

Front 30

IF YOU CUT THE URETER INSTEAD OF THE URETHRAL ARTERY, YOUR PATIENT IS GOING TO HAVE A BAD TIME!!

WTF is Dr. Dym talking about when he says water under a bridge? What is the only way to ID the branches of internal illiac with certainty?

Back 30

-Arrangement of branches is subject to wide variation.
-Note the position of the ureter under the uterine artery (“water under a bridge”).
In the laboratory, note where vessels distribute - this is the only way to identify the branches of the internal iliac with certainty

Front 31

What is the one thing you should remember about lymph drainage if you completely black-out during the practical?

Back 31

Hint 31

Front 32

Why is the first sign of ovarian cancer or testicular cancer so deadly? What makes it particularly dangerous?

Back 32

Lypmh drainage follows the reverse of the arterial supply. Remember there are pre-aortic nodes (celiac, superor mesenteric and inferior mesenteric) anterior to the aorta and there are para-aortic nodes on the sides of the aorta. Together these are called the aortic caval nodes. There are also iliac nodes following the iliac arteries. Because lymph follows the arterial supply, the testes (and ovaries) will not drain to the superficial iliac nodes! They will drain to nodes up by the renal arteries. This is important
clinically because there won’t be enlargement of superficial lymph nodes with testicular cancer as there is with say breast cancer. This makes cancer detection more difficult.

Hint 32

By the time you notice it, the cancer may already be widespread.

Front 33

Do the testes drain here?

Back 33

They will drain to nodes up by the renal arteries.

Hint 33

NOT HERE!!

Front 34

What could a lump in the groin for females indicate?

Back 34

Cancer of the uterus, or the vagina (they drain to the superfical lymph nodes) BUT NOT THE OVARIES!!

Front 35

What could you perform on a patient that has an infection/ blockage of the urethra, and you can't put in a catheter? What could go wrong with this procedure?!

Back 35

ewww.

be careful not to poke through the peritonium

Hint 35

Front 36

What does a TURP do? (Transurethral resection)

Back 36

Front 37

What could go wrong during an illegal abortion that can cause a horrible peritoneal infection?

Back 37

dirty instruments... pokes too far into the pouch of douglas (peritonium).

Hint 37

Front 38

Cancer of the vagina can show up as a lump where?

Back 38

A lump in the groin

Front 39

What helps protect your va-jayjay from fallin out?

Back 39

Front 40

When a patient has R lower quardrant pain, what could it commonly be misdiagnosed as?

Back 40

Front 41

What do you want to look for in a healthy young person that has issues with fertility?

Back 41

Want to make sure the ovaduct continues all the way through the perineal cavity

Hint 41

Can do the same for males too! Look at all the items that are being filled when you do this!

Front 42

How come we don't crush our ovaries during pregnancy?

Back 42

It moves SUPERIORLY during pregnancy

Hint 42

Front 43

Where does all the lymph drainage for the lady part go to?

Back 43

Front 44

Think about why the most common cause of death from prostate cancer is renal failure. Why is this?

Back 44

Blocks the urtethra, yo...

Front 45

Is this a boy or a girl? how can you tell?

Back 45

BOY

Hint 45

Front 46

What do you do for a vasectomy? What about a vasovasectomy?

Back 46

Hint 46

ledig cells okay... therfore testosterone is okay... but

Front 47

What sorts of things could happen if one or more of your kidneys didn't develop? Would your adrenal glands still be the same?

Back 47

pulmonary hypoplasia... ( something about amniotic fluid and the kidneys)

Hint 47

** note the right side also has a problem with rotation as well

Front 48

WTF is going on here?

Back 48

Hint 48

Front 49

Something very wrong here... what is going on? (this is actually an aortagram) Where do horshoe kidneys usually get stuck??

Back 49

Horseshoe kidney

Hint 49

Horseshoe kidneys usually get stuck under the IMA

Front 50

WTF is wrong here?

Back 50

Horseshoe kidney

Front 51

DMSA Renal scan

What the heck is this?

Back 51

Horseshoe kidney

Front 52

On the left is what a normal prenatal kidney looks like on ultrasound... and the other image obviously has something very wrong with that kidney. Why is this happening? What could cause this?!

Back 52

1/100 not always a huge emergency

Hint 52

Front 53

When someone has a "bony butt", what are you usually feeling?

Back 53

Front 54

What are the piriformis muscles and what do they do?

Back 54

Front 55

What innervates the Obturator internus muscle? Where the hell is it? What does it do?

Back 55

Front 56

Just stare at this picture for a long time, and thing about all the ways people can fracture their pelvis?

Back 56

owie

Hint 56

The pelvis can be viewed as a series of anatomical rings. There are three bony rings and four fibro-osseous rings. The major bony pelvic ring consists of parts of the sacrum, ilium, and pubis, which forms the pelvic inlet. Two smaller subsidiary rings are demonstrated as the obturator foraminae. The greater and lesser sciatic foraminae formed by the greater and lesser sciatic notches and the sacrospinous and sacrotuberous ligaments form the four fibro-osseous rings. Quite simply, the rings which are predominantly bony (i.e., the pelvic inlet and the obturator foraminae) should be regarded as brittle rings. It is not possible to break one side of the ring without breaking the other side of the ring, which in clinical terms means that if a fracture is demonstrated on one side, a second fracture should always be suspected.
Fractures of the pelvis may occur in isolation; however, they usually occur in the polytrauma patient and warrant special mention.
Owing to the large bony surfaces of the pelvis, a fracture produces an area of bone that can bleed significantly. A large hematoma may be produced, which can compress organs such as the bladder and the ureters. This blood loss may occur rapidly, reducing the circulating blood volume and, unless this is replaced, the patient will become hypovolemic and shock will develop.
Pelvic fractures may also disrupt the contents of the pelvis, leading to urethral disruption, potential bowel rupture, and nerve damage

Front 57

What may be going on in an older women that is causing her to use depends?

Back 57

Stress incontinance

Front 58

Which two ligaments help prevent upward tilting of the sacrum when weightlifting?

Back 58

Sacrospinous and sacrotuberous ligaments.

The greater sciatic foramen lies superior to the sacrospinous ligament and the ischial spine.
The lesser sciatic foramen lies inferior to the ischial spine and sacrospinous ligament between the sacrospinous and sacrotuberous ligaments.

Hint 58

Common problems with the sacro-iliac joints
The sacro-iliac joints have both fibrous and synovial components, and as with many weightbearing joints, degenerative changes may occur and cause pain and discomfort in the sacro-iliac region. In addition, disorders associated with the major histocompatibility complex antigen HLA B27, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease, can produce specific inflammatory changes within these joints.

Front 59

Birth defects are WAY more common than you think!

Back 59

Hint 59

Front 60

When do more funtional issues occur? Why does WHEN make a big difference when a child is exposed to a terotogen.

Back 60

Hint 60

The earlier in development (after implantation), the more damaging the potential teratogen may be.

Front 61

What are the different types of chromosomal disorders? How often do they cause birth defects?

Back 61

Hint 61

Front 62

What is the MOST COMMON cause of mental retardation in the states?

Back 62

Hint 62

ALCOHOL

Alcohol is a well known teratogen that results in children with fetal alcohol syndrome (FAS). Children with more subtle problems are said to have fetal alcohol effects (FAE). The combined effects of alcohol and nicotine greatly increase the risk of heart defects and cleft lip/palate.

A. Clinical Background
1. Alcoholism affects about 1-2% of women of child-bearing age
FAS
3. Maternal alcohol abuse is now considered the most common cause of mental retardation in the Western World
4. Even moderate intake periconceptually can reduce fertility

NOTE: Alcoholic women who become pregnant may also suffer from poor protein intake and certain vitamin deficiencies.


B. Pathology
1. Holoprosencephaly - disturbance in the early induction of the forebrain (prosencephalon)
2. Altered midface development (e.g. retrognathism, cyclopia)
3. Microcephaly, ocular manifestations, and other defects and behavioral and learning difficulties


C. Sensitive Period

Most severe effects take place in the first month of pregnancy. However, since brain development spans the major part of gestation, total abstinence from alcohol during pregnancy is advised.

NOTE: The potential connection between alcohol intake and problems in pregnancy has been suggested for thousands of years:
“Thou shalt conceive, and bear a son. Now therefore beware, I pray thee, and drink not wine nor strong drink.” (Judges 13: 3,4)

D. Mechanism

1. Holoprosencephaly may result from disturbance of cholesterol metabolism which disrupts the Sonic hedgehog (Shh) signaling process.
2. Ethanol induces apoptotic neurodegeneration, particularly during synaptogenesis.

Front 63

What are way we can inhibit fertility? What are was we can promote fertility? Which hormones can we manipulate? (In the female cycle)

Back 63

The Rhythm Method and Oral Contraceptives
The average menstrual cycle is 28 days in length (beginning with the first day of menses), but this may vary both between women and for an individual woman. Ovulation takes place at about midcycle, but more precisely, it occurs 14 days before the onset of the next menses. In other words, in a 26-day cycle, ovulation takes place on day 12, but in a 30-day cycle, ovulation takes place on day 16. Sperm are viable in the female reproductive tract for a few days, while mature ova are viable for only a short time after release.
For pregnancy to occur, intercourse needs to take place between approximately 5 days before ovulation and at most a day after ovulation. However, because it is not possible to predict exactly when ovulation will take place (because the date of onset of the next menses cannot be predicted with certainty), "rhythm methods" of contraception have low reliability compared with most forms of birth control. In various rhythm methods, intercourse is avoided for several days before and after the predicted date of ovulation. For example, in the Standard Days Method, women whose cycles are between 26 and 32 days in length avoid intercourse between days 8 and 19 of their cycles. In general, the rhythm method has a failure rate of several percent annually when used perfectly, and up to 25% otherwise.
With the use of oral contraceptives, most commonly a combination of an estrogen and a progestin (progesterone-like drug), cycles are controlled by the drug. Typically, hormone-containing pills are taken for 21 days, followed by a week of no pills or daily sugar pills. Pregnancy is prevented primarily by inhibition of ovulation, due to inhibition of gonadotropin release by the oral hormones. Bleeding (menstruation) occurs upon withdrawal from the hormones after 21 days. With perfect use, the annual rate of conception is 0.3%, although the failure rate is actually several percent annually.

Hint 63

Menstrual Cycle During the female menstrual cycle, changes take place in the ovaries and uterus, under the control of the hypothalamus and anterior pituitary gland. During the follicular phase, several primary follicles undergo further development in response to FSH and synthesize androgens, which are converted to estradiol under the influence of LH. Ultimately, one follicle fully matures and the others regress. The uterine endometrium proliferates in response to estradiol. Near midcyle, estradiol rises to a level that initiates positive feedback, and thus a surge in LH and FSH release by the anterior pituitary, which results in ovulation. During the ensuing luteal phase, the mature follicle becomes the corpus luteum, which secretes progesterone and estradiol. The uterus undergoes further proliferative and secretory changes. Unless pregnancy occurs, endometrial sloughing and menstruation eventually occur, marking the beginning of a new cycle. FSH, follicle-stimulating hormone; LH, luteinizing hormone.

Front 64

What can cause abnormal uterine bleeding?

Back 64

Hint 64

Normal menstrual bleeding follows the luteal phase of the cycle and is caused by the fall in gonadal hormone levels. Heavy bleeding during menses (menorrhagia) or irregular bleeding during the cycle may be caused by hormonal imbalance. Abnormal uterine bleeding can also be caused by a variety of uterine or adnexal disorders as well as systemic disorders in nonpregnant, reproductive-age women. In pregnant women, bleeding may be caused by rupture of a placental blood vessel or may foreshadow an impending miscarriage. Placenta previa, in which the placenta extends over the cervix, is often associated with bleeding after the first trimester of pregnancy. Various causes of abnormal uterine bleeding are illustrated.

Front 65

Describe the different HORMONES of the menstral cycle?

Back 65

Hint 65

The hypothalamic-pituitary-ovarian axis is characterized by both positive and negative feedback over the course of a menstrual cycle. Initially, GnRH stimulates release of LH and FSH by the pituitary; estrogen synthesized by developing ovarian follicles has negative feedback effects on the axis. However, in the late follicular phase (A), blood estradiol reaches a high level that initiates positive feedback and a surge in LH and FSH release, provoking ovulation. In the luteal phase, the system is characterized by negative feedback (B). Estradiol, progesterone, and inhibin produced by the corpus luteum have negative feedback actions on gonadotropin release. FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone.

Front 66

How quickly does the fertilization process take place?

Back 66

Upon rupture of the graafian follicle, the ovum enters the fallopian tube. If fertilization occurs, it takes place within the fallopian tube, which transports the ovum or zygote to the uterus. A zygote will have reached the blastocyst stage by day 5 and will implant in the endometrial lining at that time.

Front 67

s The testes contain convoluted seminiferous tubules, where spermatogenesis takes place, and, between the tubules, Leydig cells, which synthesize testosterone in the mature male (left panel). Sertoli cells constitute the epithelium of the tubules (right panel). Differentiation of primary spermatocytes to sperm cells begins between the Sertoli cells and is completed in the epididymis.

SOOOO... the question is... Describe where and how spermatogensis occurs, and what is so magical about it.

Back 67

Spermatogenesis is a complex process that begins with mitotic division of spermatogonia to form primary spermatocytes, along with additional spermatogonia (unlike women, in whom there are a fixed number of primary oocytes by the time of birth, the number of germ cells in men is not fixed). Meiosis of primary spermatocytes produces secondary spermatocytes, and subsequently, haploid spermatids, which undergo further differentiation to become spermatozoa. The final product, the mature spermatozoon, includes a head piece, a mitochondria-rich middle section for energy production, and a motile tail section. The head piece has a prominent acrosome containing proteolytic enzymes necessary for penetration of an ovum.

Hint 67

Front 68

What happens in Klinefelter's Syndrome (47XXY) that can make men infertile?

Back 68

Klinefelter's Syndrome
Male infertility has a large number of causes, including blockage of the vas deferens due to infection or injury; low sperm count (oligospermia) due to infections such as mumps and some sexually transmitted diseases; lack of sperm production as a result of chronic disease, hormonal problems, or injury to the testes; impotence; and exposure to toxins. In some cases, infertility may have a genetic basis. For example, Klinefelter's syndrome is characterized by the genotype 47, XXY. Patients with this syndrome are phenotypic males but have some identifiable physical characteristics including gynecomastia (breast enlargement) and are nearly always infertile (see illustration). They are hypogonadal, meaning that gonadal hormone levels are low, and as a result, gonadotropin levels are elevated and testicular size is reduced. Klinefelter's syndrome affects one to two men per 1000.

Hint 68

Testicular Failure in Klinefelter's Syndrome The presence of two X chromosomes (47, XXY genotype) results in seminiferous tubular dysgenesis and infertility, as well as primary hypogonadism (low testicular hormone levels, and as a result, high gonadotropin levels).

Front 69

So we kinda know how hormones work for women and he menstral cycle, but what about men? Describe how endocrine regulation of testicular function works

Back 69

Testicular function (both gametogenesis and steroidogenesis) is regulated by the hypothalamus and pituitary gland (Fig. 31.8). GnRH is secreted by hypothalamic nuclei into the hypophyseal portal circulation (as in females, GnRH release is pulsatile in males), and subsequently stimulates the release of LH and FSH by anterior pituitary gonadotrophs. LH stimulates the first step in testosterone synthesis (conversion of cholesterol to Δ5-pregnenolone by CYP11A10, whereas FSH acts on Sertoli cells, stimulating the synthesis of androgen-binding protein, which subsequently binds testosterone, promoting spermatogenesis in the seminiferous tubules (see Fig. 31.7). Negative feedback in the hypothalamic-pituitary-testis axis is effected by inhibition of GnRH and LH release by testosterone and by inhibition of FSH secretion via inhibin produced by Sertoli cells.

Hint 69

GnRH secreted by the hypothalamus stimulates LH and FSH secretion by the anterior pituitary. LH stimulates testosterone synthesis by the Leydig cells of the testes, whereas testosterone and FSH are required for spermatogenesis. FSH induces production of androgen-binding protein (ABG); androgen is concentrated in the tubules by binding to ABG, promoting spermatogenesis. Sertoli cells also produce inhibin, which, along with testosterone, exerts negative feedback effects on the axis (inhibin specifically inhibits FSH secretion). FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone.

Front 70

What happens in the follicular, ovulatory, and luteal phase of menstration?

Back 70

The follicular phase, characterized by proliferation of the endometrium of the uterus and development of ovarian follicles.
The ovulatory phase, during which one follicle that has fully matured ruptures and releases an ovum.
The luteal phase, characterized by transformation of follicular cells into a corpus luteum and further proliferation of the endometrium. Unless implantation of a fertilized ovum takes place, the corpus luteum regresses and menses follows, during which the proliferated endothelium is sloughed off and bleeding occurs for a period of 3 to 5 days.

Hint 70

Follicular Phase
The development of follicles within the ovary is illustrated in Figure 31.4. During each cycle, after the onset of menses (by convention, "day 1" of the cycle), several primordial ovarian follicles begin to undergo further development under the influence of FSH, and hence, the term follicular phase is used to describe the first half of the cycle. Within the developing follicles, theca interna cells secrete androgens, which are converted to estradiol by the granulosa cells of the follicles. This conversion is stimulated by LH. Estradiol causes endometrial proliferation, as well as development of glands and growth of spiral arteries within the endometrium, in preparation for possible implantation of a fertilized egg. For this reason, the follicular phase is also called the proliferative phase. In addition, estradiol promotes secretion of watery cervical mucus, through which sperm can enter the uterus. Ultimately, one of the developing follicles predominates and becomes a mature follicle (graafian follicle), and the others regress.
Ovulatory Phase
Estradiol exerts negative feedback on the hypothalamic secretion of GnRH and anterior pituitary secretion of FSH (LH is not suppressed during this period) through much of the follicular phase. Additionally, granulosa cells of developing follicles secrete a peptide hormone, inhibin, which has negative feedback effects specifically on FSH. Toward the end of the follicular phase, estradiol rises to a level at which positive feedback is triggered (Fig. 31.5). A surge in LH, and to a lesser extent, FSH, takes place and produces ovulation at midcycle, releasing a mature ovum, which is carried by ciliary action into the fallopian tube (see Fig. 31.3). Interestingly, a mature ovum is produced in alternating ovaries from month-to-month, but if a woman has only one functional ovary, that one ovary will normally produce a mature ovum monthly.
Luteal Phase
In the ensuing luteal phase of the cycle, the ruptured follicle undergoes involution, forming the corpus luteum. Progesterone and inhibin production by the corpus luteum rise, as does estradiol production to a lesser degree. Estrogens, progesterone, and inhibin now contribute to negative feedback on the hypothalamus and anterior pituitary (see Fig. 31.5). Further proliferative and secretory changes take place in the endometrium, stimulated by progesterone; the luteal phase is also called the secretory phase for this reason. In the cervix, secretions become thicker, making passage of sperm into the uterus more difficult. Conception must take place within a day or two of ovulation, because the ovum is viable for only a short period after release from the graafian follicle (normally, conception takes place while the egg is in transport within a fallopian tube). Toward the end of the luteal phase, unless pregnancy occurs, steroid and inhibin secretion fall, and menses results.

Front 71

A 25-year-old man visited his family physician because he had a "dragging feeling" in the left side of his scrotum. He was otherwise healthy and had no other symptoms. During examination, the physician palpated the left testis, which was normal, although he noted soft nodular swelling around the superior aspect of the testes and the epididymis. In his clinical notes, he described these findings as a "bag of worms" (Fig. 5.86). The bag of worms was a varicocele.

Back 71

VARICOCELE

The venous drainage of the testis is via the pampiniform plexus of veins that runs within the spermatic cord. A varicocele is a collection of dilated veins that arise from the pampiniform plexus. In many ways, they are similar to varicose veins that develop in the legs. Typically, the patient complains of a dragging feeling in the scrotum and around the testis, which is usually worse toward the end of the day.
The family physician recommended surgical treatment, with a recommendation for surgery through an inguinal incision.
A simple surgical technique divides the skin around the inguinal ligament. The aponeurosis of the external oblique muscle is divided in the anterior abdominal wall to display the spermatic cord. Careful inspection of the spermatic cord reveals the veins, which are surgically ligated.
Another option is to embolize the varicocele.
In this technique, a small catheter is placed via the right femoral vein. The catheter is advanced along the external iliac vein and the common iliac vein and into the inferior vena cava. The catheter is then positioned in the left renal vein, and a venogram is performed to demonstrate the origin of the left testicular vein. The catheter is advanced down the left testicular vein into the veins of the inguinal canal and the pampiniform plexus. Metal coils to occlude the vessels are injected, and the catheter is withdrawn.
The patient asked how blood would drain from the testis after the operation.
Although the major veins of the testis had been occluded, small collateral veins running within the scrotum and around the outer aspect of the spermatic cord permitted drainage without recurrence of the varicocele.

Front 72

A young man developed pain in his right gluteal region, in the posterior aspect of the thigh and around the posterior and lateral aspects of the leg. On further questioning, he reported that the pain also radiated over the lateral part of the foot, particularly around the lateral malleolus.

Back 72

SCIATIC NERVE COMPRESSION

The areas of pain correspond to dermatomes L4 to S3 nerves.
Over the following weeks, the patient began to develop muscular weakness, predominantly foot drop.
These findings are consistent with loss of the motor function and sensory change in the common fibular nerve, which is a branch of the sciatic nerve in the lower limb.
A computed tomography (CT) scan of the abdomen and pelvis revealed a mass in the posterior aspect of the right side of the pelvis. The mass was anterior to the piriformis muscle and adjacent to the rectum.
On the anterior belly of the piriformis muscle, the sciatic nerve is formed from the roots of L4 to S3 nerves. The mass in the patient's pelvis compressed this nerve, producing his sensory and motor dysfunction.
During surgery, the mass was found to be a benign nerve tumor and was excised. This patient had no long-standing neurological deficit.

Front 73

A young woman visited her family practitioner because she had mild upper abdominal pain. An ultrasound demonstrated gallstones within the gallbladder, which explained the patient's pain. However, when the technician assessed the pelvis, she noted a mass behind the bladder, which had sonographic findings similar to a kidney.

What did the sonographer do next?

Back 73

PELVIC KIDNEY

Having demonstrated this pelvic mass behind the bladder, the sonographer assessed both kidneys. The patient had a normal right kidney. However, the left kidney could not be found in its usual place. The technician diagnosed a pelvic kidney.
A pelvic kidney can be explained by the embryology. The kidneys develop from a complex series of structures that originate adjacent to the bladder within the fetal pelvis. As development proceeds and the functions of the various parts of the developing kidneys change, they attain a superior position in the upper abdomen adjacent to the abdominal aorta and inferior vena cava, on the posterior abdominal wall. A developmental arrest or complication may prevent the kidney from obtaining its usual position. Fortunately, it is unusual for patients to have any symptoms relating to a pelvic kidney.
This patient had no symptoms attributable to the pelvic kidney and she was discharged.

Front 74

A 65-year-old man was examined by a surgical intern because he had a history of buttock pain and impotence. On examination he had a reduced peripheral pulse on the left foot compared to the right. On direct questioning, the patient revealed that he experienced severe left-sided buttock pain after walking 100 yards. After a short period of rest, he could walk another 100 yards before the same symptoms recurred. He also noticed that over the past year he was unable to obtain an erection. He smoked heavily and was on no other drugs or treatment.

How does blood get to the gluteal muscle? How will the patient be treated?

Back 74

LEFT COMMON ILIAC ARTERY OBSTRUCTION

The pain in the left buttock is ischemic in nature. He gives a typical history relating to lack of blood flow to the muscles. A similar finding is present when muscular branches of the femoral artery are occluded or stenosed. Such patients develop similar (ischemic) pain in the calf muscles called intermittent claudication.
How does the blood get to the gluteal muscles?
Blood arrives at the aortic bifurcation and then passes into the common iliac arteries, which divide into the internal and external iliac vessels. The internal iliac artery then divides into anterior and posterior divisions, which in turn give rise to vessels that leave the pelvis by passing through the greater sciatic foramen and supply the gluteal muscles. The internal pudendal artery also arises from the anterior division of the internal iliac artery and supplies the penis.
The patient's symptoms occur on the left side, suggesting that an obstruction exists on that side only.
Because the patient's symptoms occur on the left side only, the lesion is likely in the left common iliac artery (Fig. 5.88) and is preventing blood flow into the external and internal iliac arteries on the left side.
"How will I be treated?" asked the patient.
The patient was asked to stop smoking and begin regular exercise. Other treatment options include unblocking the lesion by ballooning the blockage to re-open the vessels or by a surgical bypass graft.
Stopping smoking and regular exercise improved the patient's walking distance. The patient underwent the less invasive procedure of ballooning the vessel (angioplasty) and as a result he was able to walk unhindered and to have an erection.

Hint 74

Digital subtraction aortoiliac angiogram. A. Normal circulation pattern. B. Occluded left common iliac artery

Front 75

A 50-year-old woman was admitted to hospital for surgical resection of the uterus (hysterectomy) for cancer. The surgeon was also going to remove all the pelvic lymph nodes and carry out a bilateral salpingo-oophorectomy (removal of uterine tubes and ovaries). The patient was prepared for this procedure and underwent routine surgery. Twenty-five hours after surgery, it was noted that the patient had passed no urine and her abdomen was expanding. An ultrasound scan demonstrated a considerable amount of fluid within the abdomen. Fluid withdrawn from the abdomen was tested and found to be urine.

How could this have happened?

Back 75

IATROGENIC URETERIC INJURY

It was postulated that this patient's ureters had been damaged during the surgery.
The pelvic part of the ureter courses posteroinferiorly and external to the parietal peritoneum on the lateral wall of the pelvis anterior to the internal iliac artery. It continues in its course to a point approximately 2 cm superior to the ischial spine and then passes anteromedially and superior to the levator ani muscles. Importantly, the ureter closely adheres to the peritoneum. The only structure that passes between the ureter and the peritoneum in men is the ductus deferens. In women, however, as the ureter descends on the pelvic wall, it passes under the uterine artery. The ureter continues close to the lateral fornix of the vagina, especially on the left, and enters the posterosuperior angle of the bladder. It was at this point that the ureter was inadvertently damaged.
Knowing the anatomy and recognizing the possibility of ureteric damage enabled the surgeons to re-establish continuity of the ureter surgically. The patient was hospitalized a few days longer than expected and made an uneventful recovery.

Front 76

A 25-year-old woman was admitted to the emergency department with a complaint of pain in her right iliac fossa. The pain had developed rapidly over approximately 40 minutes and was associated with cramps and vomiting. The surgical intern made an initial diagnosis of appendicitis.

Whaaaat else could it be? What else should the surgical intern check for so his ass doesn't get sued?

Back 76

ECTOPIC PREGNANCY

The typical history for appendicitis is a central abdominal, colicky (intermittent waxing and waning) pain, which over a period of hours localizes to become a constant pain in the right iliac fossa. The central colicky pain is typical for a poorly localized visceral type pain. As the parietal peritoneum becomes inflamed, the pain becomes localized. Although this patient does have right iliac fossa pain, the history is not typical for appendicitis (although it must be remembered that patients may not always have a classical history for appendicitis).
The surgical intern asked a more senior colleague for an opinion.
The senior colleague considered other anatomical structures that lie within the right iliac fossa as a potential cause of pain. These include the appendix, the cecum, and the small bowel. Musculoskeletal pain and referred pain could also be potential causes. In women, pain may also arise from the ovary, fallopian tube, and uterus. In a young patient, diseases of these organs are rare. Infection and pelvic inflammatory disease may occur in the younger patient and need to be considered.
The patient gave no history of these disorders.
Upon further questioning, however, the patient revealed that her last menstrual period was 6 weeks before this examination. The senior physician realized that a potential cause of the abdominal pain was a pregnancy outside the uterus (ectopic pregnancy). The patient was rushed for an abdominal ultrasound, which revealed no fetus or sac in the uterus. She was also noted to have a positive pregnancy test. The patient underwent surgery and was found to have a ruptured fallopian tube caused by an ectopic pregnancy.
Whenever a patient has apparent pelvic pain, it is important to consider the gender-related anatomical differences. Ectopic pregnancy should always be considered in women of childbearing age.

Front 77

A 35-year-old woman visited her family practitioner because she had a "bloating" feeling and an increase in abdominal girth. The family practitioner examined the lower abdomen, which revealed a mass that extended from the superior pubic rami to the level of the umbilicus. The superior margin of the mass was easily palpated, but the inferior margin appeared to be less well defined.

Back 77

UTERINE TUMOR

This patient has a pelvic mass.
When examining a patient in the supine position, the observer should uncover the whole of the abdomen.
Inspection revealed a bulge in the lower abdomen to the level of the umbilicus. Palpation revealed a hard and slightly irregular mass with well-defined superior and lateral borders and a less well-defined inferior border, giving the impression that the mass continued into the pelvis. The lesion was dull to percussion. Auscultation did not reveal any abnormal sounds.
The doctor pondered which structures this mass may be arising from. When examining the pelvis, it is important to remember the sex differences. Common to both men and women are the rectum, bowel, bladder, and musculature. Certain pathological states are also common to both sexes, including the development of pelvic abscesses and fluid collections.
In men, the prostate cannot be palpated transabdominally, and it is extremely rare for it to enlarge to such an extent in benign diseases. Aggressive prostate cancer can spread throughout the whole of the pelvis, although this is often associated with bowel obstruction and severe bladder symptoms.
In women, a number of organs can develop large masses, including the ovaries (solid and cystic tumors), the embryological remnants within the broad ligaments, and the uterus (pregnancy and fibroids).
The physician asked further questions.
It is always important to establish whether the patient is pregnant (occasionally, pregnancy may come as a surprise to the patient).
This patient's pregnancy test was negative. After the patient emptied her bladder, there was no change in the mass. The physician thought the mass might be a common benign tumor of the uterus (fibroid). To establish the diagnosis, he obtained an ultrasound scan of the pelvis, which confirmed that the mass stemmed from the uterus.
The patient was referred to a gynecologist, and after a long discussion regarding her symptomatology, fertility, and risks, the surgeon and the patient agreed that a hysterectomy (surgical removal of the uterus) would be an appropriate course of therapy.
The patient sought a series of opinions from other gynecologists, all of whom agreed that surgery was the appropriate option.
The fibroid was removed with no complications.

Front 78

How can you tell which one is the vagina and which one is part of the cervix?

Back 78

Front 79

Which one is the mammary gland, and which one is the labia? How can you tell which is which?

Back 79

Front 80

How can you tell which one is the urethra and which one is the clitoris? What features does each have?

Back 80

Front 81

What are the THECAS!?!

Back 81

Front 82

What is really going on in the different layers of the ovary?

Back 82

Front 83

What is so special about the uterine tube? What two cell types line the tube?

Back 83

Front 84

What is the SUPER impoertan job of the SERTOLI cells? Hint: how come our immune system doesnt FREAK OUT and destroy the testis?

Back 84

Front 85

The skeletal muscle here is CLASSIC of which gland here?

Back 85

cowpers glands (bulberurethreal)

we dion't have a friggin clue why/ how it gets there!

Front 86

What is so useful about this pampiniform plexus?

Back 86

helps cool down (counter current heat exchange)

Front 87

What the hell is the difference between spermatogensis and spermeogenesis?

Back 87

spermeogenesis is elongation of round spermatid to sperm

Front 88

What is sheehan's syndrome?

Back 88

ALSO patients have High releasing hormone levels due to a lack of negative feedback

Hint 88

Front 89

What can cause Sheehans syndrome?

Back 89

Sheehan syndrome, also known as Simmonds' syndrome or postpartum hypopituitarism or postpartum pituitary necrosis, is hypopituitarism (decreased functioning of the pituitary gland), caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth. Pituitary damage unrelated to pregnancy is called Simmonds' disease.

Hint 89

Most common initial symptoms of Sheehan's syndrome are agalactorrhea (absence of lactation) and/or difficulties with lactation.[3] Many women also report amenorrhea or oligomenorrhea after delivery.[3] In some cases, a woman with Sheehan syndrome might be relatively asymptomatic, and the diagnosis is not made until years later, with features of hypopituitarism.[3] Such features include secondary hypothyroidism with tiredness, intolerance to cold, constipation, weight gain, hair loss and slowed thinking, as well as a slowed heart rate and low blood pressure. Another such feature is secondary adrenal insufficiency, which, in the rather chronic case is similar to Addison's disease with symptoms including fatigue, weight loss, hypoglycemia (low blood sugar levels), anemia and hyponatremia (low sodium levels). Such a woman may, however, become acutely exacerbated when her body is stressed by, for example, a severe infection or surgery years after her delivery, a condition equivalent with an Addisonian crisis.[3] Gonadotropin deficiency will often cause amenorrhea, oligomenorrhea, hot flushes, or decreased libido.[3] Growth hormone deficiency causes many vague symptoms including fatigue and decreased muscle mas

Front 90

DONT FORGET THAT THESE ARE IN THE SAME PLANE!!

Back 90

In the anatomical position, the pelvis is oriented so that the front edge of the top of the pubic symphysis and the anterior superior iliac spines lie in the same vertical plane (Fig. 5.26). As a consequence, the pelvic inlet, which marks the entrance to the pelvic cavity, is tilted to face anteriorly, and the bodies of the pubic bones and the pubic arch are positioned in a nearly horizontal plane facing the ground.

Front 91

how do nerves from the spine get in to the pelvis?

Back 91

Hint 91

Apertures in the pelvic wall
Each lateral pelvic wall has three major apertures through which structures pass between the pelvic cavity and other regions:
the obturator canal;
the greater sciatic foramen; and
the lesser sciatic foramen.
Obturator canal
At the top of the obturator foramen is the obturator canal, which is bordered by the obturator membrane, the associated obturator muscles, and the superior pubic ramus (Fig. 5.31). The obturator nerve and vessels pass from the pelvic cavity to the thigh through this canal.
Greater sciatic foramen
The greater sciatic foramen is a major route of communication between the pelvic cavity and the lower limb (Fig. 5.31). It is formed by the greater sciatic notch in the pelvic bone, the sacrotuberous and the sacrospinous ligaments, and the spine of the ischium.

The piriformis muscle passes through the greater sciatic foramen, dividing it into two parts.
The superior gluteal nerves and vessels pass through the foramen above the piriformis.
Passing through the foramen below the piriformis are the inferior gluteal nerves and vessels, the sciatic nerve, the pudendal nerve, the internal pudendal vessels, the posterior femoral cutaneous nerves, and the nerves to the obturator internus and quadratus femoris muscles.
Lesser sciatic foramen
The lesser sciatic foramen is formed by the lesser sciatic notch of the pelvic bone, the ischial spine, the sacrospinous ligament, and the sacrotuberous ligament (Fig. 5.31). The tendon of the obturator internus muscle passes through this foramen to enter the gluteal region of the lower limb.
Because the lesser sciatic foramen is positioned below the attachment of the pelvic floor, it acts as a route of communication between the perineum and the gluteal region. The pudendal nerve and internal pudendal vessels pass between the pelvic cavity (above the pelvic floor) and the perineum (below the pelvic floor), by first passing out of the pelvic cavity through the greater sciatic foramen, then looping around the ischial spine and sacrospinous ligament to pass through the lesser sciatic foramen to enter the perineum.

Front 92

How do we know if the baby is going to be able to fit through mom's who-ha or if we are going to need a C section?

Back 92

Pelvic measurements in obstetrics
In pregnancy, if it is thought that the size and position of the fetal head could cause problems in childbirth, accurate transverse and sagittal measurements of the mother's pelvic inlet and outlet can help in predicting the likelihood of a successful vaginal delivery. These measurements include:
the sagittal inlet (between the promontory and the top of the pubic symphysis);
the maximum transverse diameter of the inlet;
the bispinous outlet (the distance between ischial spines); and
the sagittal outlet (the distance between the tip of the coccyx and the inferior margin of the pubic symphysis).
The acceptable values for these are 11, 11.5, 9, and 10 cm, respectively.
These measurements can be obtained using plain radiographs and computed tomography scans. Both these techniques use ionizing radiation, and even a low dose carries a potential risk to the mother and fetus. Newer techniques include magnetic resonance imaging, which carries no radiation risk for the fetus or mother

Front 93

What are all the muscles involved in POOPING

Back 93

Defecation
At the beginning of defecation, intra-abdominal pressure is increased by muscular contraction of the quadratus lumborum, the rectus abdominis, the external and internal oblique, and the transversus abdominis muscles. The diaphragm is stabilized by the closure of the larynx.
The puborectalis muscle surrounding the anorectal junction relaxes to allow straightening of the anorectal angle (the puborectal sling usually produces an angle of about 90° between the rectum and the anal canal so that it is closed off). The anorectal angle normally acts as a "pinch valve" to prevent defecation. In defecation the anorectal angle increases to about 130°-140°; as a result the anal canal straightens and feces can be evacuated.
In addition, the external anal sphincter relaxes and so shortens the anal canal. (When contracted, the external anal sphincter accentuates the action of the puborectalis by pulling the anorectal junction forward to further increase the anorectal angle.)
The fatty tissue of the ischio-anal fossa allows for changes in the position and size of the anal canal and anus during defecation. During evacuation, the anorectal junction moves down and back and the pelvic floor usually descends slightly.
The internal anal sphincter, which usually acts to close off the upper and middle portions of the anal canal, relaxes to allow the passage of feces.
The circular muscles of the rectal wall undergo a wave of contraction to push feces toward the anus.
As feces emerge from the anus, the longitudinal muscles of the rectum and levator ani bring the anal canal back up, the feces are expelled, and the anus and rectum return to their normal positions.

Front 94

How are the muscles in the deep perineal pouch different in men versus women?

Back 94

Front 95

What can be detected with a digital rectal exam?

Back 95

Digital rectal examination
A digital rectal examination (DRE) is a straightforward procedure performed by a clinician and should be undertaken by all physicians at some stage during their training.
The procedure is performed by placing the gloved and lubricated index finger into the rectum through the anus. The anal mucosa should be palpated for mass lesions knowing that a small percentage of colorectal tumors may be directly palpable. In the female the posterior wall of the vagina and the cervix can be palpated. In the male the prostate should be palpated. The central sulcus and left and right lobes are easily felt and any extraneous nodules or masses will be easily detected.
In many instances the digital rectal examination may be followed by proctoscopy or colonoscopy. An ultrasound probe may be placed into the rectum to assess the gynecological structures in females and the prostate in the male before performing a prostatic biopsy

Hint 95

Carcinoma of the colon and rectum
Carcinoma of the colon and rectum (colorectum) is a common and lethal disease. Recent advances in surgery, radiotherapy, and chemotherapy have only slightly improved 5-year survival rates.
The biologic behavior of tumors of the colon and rectum is relatively predictable. Most of the tumors develop from benign polyps, some of which undergo malignant change. The overall prognosis is related to:
the degree of tumor penetration through the bowel wall;
the presence or absence of lymphatic dissemination; and
the presence or absence of systemic metastases.
Given the position of the colon and rectum in the abdominopelvic cavity and its proximity to other organs, it is extremely important to accurately stage colorectal tumors: a tumor in the pelvis, for example, could invade the uterus or bladder. Assessing whether spread has occurred may involve ultrasound scanning, computed tomography, and magnetic resonance imaging.

Front 96

Where does all tthis fit in to the pelvis? What about the sympathetic nerve trunk?

Where can we find the sciatic nerve? What about the pudendal nerve?

Back 96

Hint 96

Sciatic nerve
The sciatic nerve is the largest nerve of the body and carries contributions from L4 to S3 (Figs. 5.59 and 5.60). It:
forms on the anterior surface of the piriformis muscle and leaves the pelvic cavity through the greater sciatic foramen inferior to piriformis;
passes through the gluteal region into the thigh, where it divides into its two major branches, the common fibular nerve (common peroneal nerve) and the tibial nerve-dorsal divisions of L4, L5, S1, and S2 are carried in the common fibular part of the nerve and the ventral divisions of L4, L5, S1, S2, and S3 are carried in the tibial part;
innervates muscles in the posterior compartment of the thigh and muscles in the leg and foot; and
carries sensory fibers from the skin of the foot and lateral leg.
Pudendal nerve
page 465

page 466
The pudendal nerve forms anteriorly to the lower part of piriformis muscle from ventral divisions of S2 to S4 (Figs. 5.59 and 5.60). It:
leaves the pelvic cavity through the greater sciatic foramen, inferior to the piriformis muscle, and enters the gluteal region;
courses into the perineum by immediately passing around the sacrospinous ligament, where the ligament joins the ischial spine, and through the lesser sciatic foramen (this course takes the nerve out of the pelvic cavity, around the peripheral attachment of the pelvic floor, and into the perineum);
is accompanied throughout its course by the internal pudendal vessels; and
innervates skin and skeletal muscles of the perineum, including the external anal and external urethral sphincters

Front 97

What nerves would you have to cut so that these muscles no longer work? What would you not be able to do anymore?

Back 97

Hint 97

Front 98

What nerves would you have to cut so that these muscles no longer work? What would you not be able to do anymore?

Back 98

Hint 98

Front 99

Back 99

Hint 99

Front 100

What other muscles are near this?

Back 100

Hint 100

Front 101

What is probably going to happen to this poor fellow?

Back 101

Urethral rupture
Urethral rupture may occur at a series of well-defined anatomical points.
The commonest injury is a rupture of the proximal spongy urethra below the perineal membrane. The urethra is usually torn when structures of the perineum are caught between a hard object (e.g., a steel beam or cross bar of a bicycle) and the inferior pubic arch. Urine escapes through the rupture into the superficial perineal pouch and descends into the scrotum and onto the anterior abdominal wall deep to the superficial fascia.
In association with severe pelvic fractures, urethral rupture may occur at the prostatomembranous junction above the deep perineal pouch. The urine will extravasate into the true pelvis.
The worst and most serious urethral rupture is related to serious pelvic injuries where there is complete disruption of the puboprostatic ligaments. The prostate is dislocated superiorly not only by the ligamentous disruption but also by the extensive hematoma formed within the true pelvis. The diagnosis can be made by palpating the elevated prostate during a digital rectal examination.

Hint 101

Front 102

Back 102

ouch

Front 103

What does this same nerve look like in females?

Back 103

Hint 103

Front 104

PREGNANCY IS A HYPERCOAGULATABLE STATE!! What does this mean for mom (Good and bad?)

Back 104

Higher risk for DVT, but good during birth so mom doesn't lose too much blood.

Hint 104

blood is thinner, crit level goes down.

Front 105

DEFINITE TEST QUESTION: During pregnancy... if the mom has HYDRONEPHROSIS!!! The R side gets a LOT larger than the left side. Why?! (2 reasons)

Back 105

1. Uterus is dextrorotated- sigmoid is usually on one side- uterus pushed more on right side.
2. Whats the other one?

Hint 105

The dilatation is often more prominent on the right side.

Front 106

TEST QUESTION: ***UNDERSTAND TSH and B HcG—look VERY similar. Why is this?

Back 106

Same beta subunits... Mom has higher metabolisim.... looks very similar... something like that. get more details

Front 107

Babies are usually very hypoglycemic after birth. Why is this?

Back 107

Babies can crash after birth m(neonates) cause they are so used to having lots of glucose pumped from mom. Have high levels of insulin.

Baby has to make its own insulin insulin is also a growth factor too! This is why I was a ginourmous baby.

Front 108

Which TERMINAL DELETION is the most common?

Hint-- it is a deletion of the short arm of chromosome 5. Besides a smaller head, what other symptoms would you see?

Back 108

Cri du chat syndrome

weak cat-like cry when they are born; microcephaly; severe mental retardation, heart anomalies

Front 109

Which one is a ....

ISOCHROMOSOME?
DUPLICATION?

Back 109

A. RECIPROCAL TRANSLOCATION
B. TERMINAL DELETION
D. TERMINAL DELETION
E. PARACENTRIC INVERSION
F. ISOCHROMOSOME

Hint 109

TRANSLOCATIONS (Figure 2A)
• -Swapping of DNA from one chromosome to another nonhomologous chromosome due to breakage
• -Breakage may be induced by radiation, drugs, chemicals, viruses
• -Severity of resulting phenotypic defect depends on the nature of the translocation
 ++Balanced translocation: the DNA is equally exchanged between chromosomes and none is lost or added. May have no phenotypic effect, but chromosome may be unstable during gametogenesis; therefore, there is a risk of passing an unbalanced chromosome to a conceptus.
 ++Unbalanced translocation: DNA is added or lost. 3-4% of people with Down syndrome have the extra Chr. 21 attached to another chromosome.

TERMINAL DELETIONS (Figure 2B)
• -e.g. partial terminal deletion of short arm of chromosome 5 causes cri du chat syndrome
 ->weak cat-like cry; microcephaly; severe mental retardation, heart anomalies

DUPLICATIONS (Figure 2D)
• -Part of a chromosome is duplicated and exists as a tandem repeat within a chromosome; attached to a chromosome; or as a separate fragment.
• -More common than deletions, but typically less harmful (no loss of DNA).

INVERSIONS (Figure 2E)
• -Segment of chromosome reversed
• -PARACENTRIC = confined to single arm of chromosome
• -PERICENTRIC = both arms, including centromere; can cause aberrant crossing over and segregation during meiosis

ISOCHROMOSOMES (Figure 2F)
-Centromere divides transversely instead of longitudinally, so short and long arms separate and effectively duplicate.
-Most common structural defect of X chromosome

Front 110

What type of single gene mutation does he have? What is the Function of this gene?

Back 110

Hint 110

Front 111

What are some consequences of these? What kinds of recessive disease can happen to someone with a problem in their CYP21 gene?

Back 111

Front 112

There are several maternal factors which can affect fetal development: genetics, age, metabolism (pharmacokinetics), nutrition, stress, and disease.

MATERNAL FACTORS AS TERATOGENS. What are some?

Back 112

folic acid deficiency hypothyroidism
PKU
hyperthermia
Diabetus Mellatus
Pre-eclampsia

**These more general maternal effects may be different from those which affect the placenta or fetus directly.

Hint 112

PRE-ECLAMPSIA

A. Clinical Background
1. Preeclampsia (aka, toxemia of pregnancy) is a disorder that occurs only during pregnancy. It is a rapidly progressive condition that occurs during mid to late pregnancy (late 2nd and 3rd trimesters) and is characterized by high blood pressure and the presence of protein in the urine. Swelling, sudden weight gain, headaches and changes in vision are important symptoms.
2. Worldwide, preeclampsia kills at least 76,000 women and fetuses annually. In the United States, it occurs in ~8% of pregnancies and accounts for at least 15% of premature births. (Currently, the only cure for the condition is to induce labor.)
3. Preeclampsia is more common in a woman’s first pregnancy and in women whose mothers or sisters had preeclampsia. The risk is higher among women carrying multiple babies, in teenage mothers, and in women over 40. Other risk factors include pre-existing renal disease or high blood pressure before becoming pregnant.

4. Recent evidence from the University of Pittsburgh (Bodnar et al, Am J Epidemiol 2006)) suggests that taking multivitamins in the periconceptual time period reduces a woman’s chance of developing preeclampsia by 45%. If near-ideal bodyweight is maintained, the reduction in risk is 72%; obese women (20% over ideal weight) saw no reduction in risk.
B. Pathology (“Diabetic Embryopathy”)
1. Preeclampsia can prevent the placenta from getting sufficient blood supply, thereby starving the fetus leading to IUGR and associated problems.
2. A few women develop eclampsia (seizures caused by toxemia) which is very serious for both mother and baby.
C. Mechanism
The mechanism underlying preeclampsia is not known. Dysfunction of maternal uterine endothelial cells (those that would participate in placenta formation) is emerging as prominent component of the condition. Excess placental-derived VEGF receptor 1 and a novel placenta-derived soluble TGF-β co-receptor are found in the sera of preeclamptic women.

DIABETES MELLITUS (MATERNAL)

A. Clinical Background
1. The incidence of congenital anomalies is 2X-3X greater in offspring from diabetic mothers (especially if glucose levels are poorly controlled); this includes Type 1 & 2 plus gestational diabetes mellitus (i.e. glucose intolerance first detected during pregnancy)
2. About 40% of the perinatal deaths in these offspring are the result of congenital anomalies.
3. The risk can be reduced by achieving good control before conception; otherwise, the risk increases proportionate to the mother’s hyperglycemia
B. Pathology (“Diabetic Embryopathy”)
Type 1 diabetes mellitus can result in excessive fetal size (macrosomia) leading to increased risk of difficult labor. 1/8 diabetic LGA attributable to glucose intolerance
1. macrosomia - large infant (LGA)
2. holoprosencephaly - failure of forebrain to divide into hemispheres
3. sacral agenesis
C. Mechanism
The teratogenic mechanism of diabetic embryopathy is not known. Presumably maternal hyperglycemia spills over into the fetus causing increased insulin levels in the fetus.

Front 113

Constriction of the uterine environment may cause reduction defects of the limbs or face. MECHANICAL FACTORS AS TERATOGENS: What are they? Name some.

Back 113

Maternal - first pregnancy, small uterus, myometrial tumors
Fetal Membranes - oligohydramnios (significant reduction in amniotic fluid), amniotic bands
Twins/Multiple Fetuses – may cause extrinsic impingements

Hint 113

AMNIOTIC BANDS
• Form as the result of tears in the extraembryonic membranes
• Can constrict digits or limbs and cause amputations

OLIGOHYDRAMNIOS (LESS THAN 500 ML AMNIOTIC FLUID)
• Often due to renal agenesis
• Can cause deformations similar to those caused by uterine malformations

Front 114

A DEFORMATION( alteration in shape/ position of a previously normal structure) is more likely to occur during the FETAL period. What is the most common cause of deformation in newborns? Why is this?

Back 114

UTERINE ENVIRONMENT
A deformation is an alteration in shape and/or position of a previously normal structure and is more likely to occur during the fetal period. UTERINE CONSTRAINT is the most common cause of deformation in newborns. This is particularly due to the fact that between the 35th -38th weeks of gestation, the rapidly increasing growth of the fetus outpaces the growth of the uterus while at the same time there is a relative decrease in amniotic fluid which acts as a cushion. Constriction of the uterine environment may cause reduction defects of the limbs or face. Such causes include:

Maternal - first pregnancy, small uterus, myometrial tumors
Fetal Membranes - oligohydramnios (significant reduction in amniotic fluid), amniotic bands
Twins/Multiple Fetuses – may cause extrinsic impingements

Front 115

INFECTIOUS AGENTS AS TERATOGENS: What is the only anti-body able to cross the placenta? What are some terotogenic infectious agents?

Back 115

Rubella, syphilis, toxoplasmosis

Hint 115

After PRIMARY infection during pregnancy, certain infectious agents can enter the blood, establish infection in the placenta, and then invade the fetus. The fetal immune system is far from being mature enough to combat infectious disease. While maternal antibodies (IgG) do cross the placenta to protect the fetus, this provides only limited passive immunity. For this reason, a striking feature of in utero infections is that generally they are mild or unnoticed by the pregnant woman, yet may damage or kill the fetus. Another feature is that generally in utero infections follow primary infections of the mother (i.e. non-immune women of child-bearing age).

RUBELLA VIRUS (GERMAN OR THREE DAY MEASLES)
A. Clinical Background
1. Congenital rubella infection is a prototype of infective teratogenesis
2. 1941 epidemic highlighted teratogenic effects
3. 1964-65 rubella epidemic resulted in 20,000 cases of congenital rubella
4. Vaccinations have been available since 1969; unvaccinated mothers continue to be susceptible (today, only about 10 cases are reported each year)
B. Pathology
Causes a classic triad of signs (“rubella syndrome”): deafness, cataracts, and heart malformations (esp. patent ductus arteriosus/PDA).
C. Sensitive Period
This virus affects women and their fetuses especially during the first trimester.
First month infection - 50% affected
Second month infection - 20% affected
Third month infection - 7%
D. Mechanism
1. Rubella virus has a primary effect on blood vessels in developing organs
2. Rubella virus also can inhibit cell mitosis

OTHERS: syphilis, toxoplasmosis

Front 116

TAKE YOUR TIME!!! And look @ this chart... What is the relationship between the types of malformations, and stage of embryonic/ fetal development?

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Front 117

With so many things that have the potential to go wrong, it is important to Identify potential tetratogens... but why is it so damn hard to do?

Back 117

1. It is not always easy to identify something as a teratogen:
a. complicated nature of teratogenesis
b. many congenital deformities are multifactorial (i.e. genetics + environment)
c. very few drugs increase the total malformation rate by a factor of two or more; most known human teratogens are associated with low rates of malformation (this means that a large number of cases needs to be identified to establish a causal relationship)
d. syndromes they cause are not always pathognomonic (i.e. not unique to the agent)

2. Major abnormalities in reproduction and development may occur spontaneously (background incidence of major malformations ~3%). It is possible that an adverse effect is due to chance.

Front 118

Name some environmental teratogens

Back 118

ENVIRONMENTAL CHEMICALS AS TERATOGENS

While there are increasing concerns about environmental chemicals, most have not been implicated as teratogens in humans. Environmental exposures will vary according to general, home, and work.


ORGANIC MERCURY (Methylmercury)

A. Clinical Background

During 1956, in a small fishing village of Minamata Bay, Japan, many babies were born with severe CNS disorders in numbers too great to be coincidental (“Minamata Disease”). Adults also became ill with stomach aches so severe the condition was called “ouch-ouch disease.” It was determined they were eating shellfish from the bay which was contaminated with methylmercury, formed by plankton exposed to mercury dumped from a nearby chemical plant.

B. Pathology

Organic mercury (methylmercury) causes neurological and behavioral disturbances resembling cerebral palsy (brain damage, mental retardation, blindness)


C. Mechanism

Abnormal neuronal cytoarchitecture suggests a derangement of neuronal migration during fetal development.

OTHERS - polychorinated biphenyls (PCB’s), dioxin, lead


RECREATIONAL DRUGS AS TERATOGENS

ALCOHOL
Alcohol is a well known teratogen that results in children with fetal alcohol syndrome (FAS). Children with more subtle problems are said to have FETAL ALCOHOL EFFECTS (FAE). The combined effects of alcohol and nicotine greatly increase the risk of heart defects and cleft lip/palate.

A. Clinical Background
1. Alcoholism affects about 1-2% of women of child-bearing age
2. MATERNAL ALCOHOL ABUSE IS NOW CONSIDERED THE MOST COMMON CAUSE OF MENTAL RETARDATION IN THE WESTERN WORLD
3. Even moderate intake periconceptually can reduce fertility

NOTE: ALCOHOLIC WOMEN WHO BECOME PREGNANT MAY ALSO SUFFER FROM POOR PROTEIN INTAKE AND CERTAIN VITAMIN DEFICIENCIES.

B. Pathology
1. Holoprosencephaly - disturbance in the early induction of the forebrain (prosencephalon)
2. Altered midface development (e.g. retrognathism, cyclopia)
3. Microcephaly, ocular manifestations, and other defects and behavioral and learning difficulties


C. Sensitive Period

Most severe effects take place in the first month of pregnancy. However, since brain development spans the major part of gestation, total abstinence from alcohol during pregnancy is advised.

NOTE: THE POTENTIAL CONNECTION BETWEEN ALCOHOL INTAKE AND PROBLEMS IN PREGNANCY HAS BEEN SUGGESTED FOR THOUSANDS OF YEARS:

D. Mechanism
1. Holoprosencephaly may result from disturbance of cholesterol metabolism which disrupts the Sonic hedgehog (Shh) signaling process.
2. Ethanol induces apoptotic neurodegeneration, particularly during synaptogenesis.
OTHERS: Cigarette smoking (NOTE: nicotine from smoking will also enter breast milk); caffeine

ILLEGAL DRUGS AS TERATOGENS

Since 1985, at least 240 women in the US have been criminally prosecuted for using illegal drugs or alcohol during pregnancy!!

COCAINE
A. Clinical Background
1. Cocaine is one of the most commonly abused illicit drugs
2. In some major US cities, up to 20% of babies are born to mothers who abuse cocaine
3. Recent report following 11,000 newborns exposed to cocaine in utero found no increase in external physical abnormalities at birth
4. May be associated with abnormal neurobehavioral development postnatally (decreased IQ and language skills)

NOTE: Mothers who abuse cocaine often abuse other drugs (e.g. alcohol, tobacco, and heroin)
B. Pathology

1. IUGR
2. CNS problems - microcephaly, infarction of cerebral cortex
3. Cardiovascular malformations
4. Fetal addiction (cocaine readily crosses the placenta)
5. Postnatal neurobehavioral disturbances

C. Mechanism
1. vasoconstrictive effects on placenta

Hint 118

MEDICINAL DRUGS AS TERATOGENS

MOST DRUGS (BOTH PRESCRIPTION AND OTC) TAKEN BY PREGNANT WOMEN CAN CROSS THE PLACENTA AND EXPOSE THE DEVELOPING EMBRYO OR FETUS TO THEIR PHARMACOLOGIC AND TERATOGENIC EFFECTS. While drugs vary considerably in their teratogenicity, only a few drugs have been positively implicated as human teratogenic agents. [Table 4] However, it is best for women to avoid using medications during the first trimester unless there is a strong medical reason for its use, and then only if it is recognized as reasonably safe for the human embryo.

THALIDOMIDE
For decades it was believed that the placenta served as a barrier that protected the fetus from the adverse effects of drugs. The thalidomide disaster drastically changed this perspective. The suffering it caused has prompted the belief that every new drug has the potential to be a “new thalidomide.”

A. Clinical Background

1954 - thalidomide created in West Germany
1956 - first child born with birth defects (child had no ears; cause unknown at the time)
1957 - marketed as a non-barbiturate sedative (sold in over 20 countries but not US!)
1961 - clinical reports published indicating the drug as the cause of limb and bowel malformation
1962 - drug removed from market; 12,000 babies were affected (“thalidomide babies”); up to 40% died soon after birth
1998 - FDA approves Celgene’s application to sell thalidomide for the treatment of a certain form of leprosy; to prevent any fetal exposure, there are very rigorous restrictions on prescriptions called the System for Thalidomide Education and Prescribing Safety or “STEPS Program”!!
present- clinical investigations into using thalidomide for other conditions (e.g. cancer, HIV wasting, Crohn’s disease, certain types of blindness); also research on safer analogues of thalidomide

B. Pathology
1. Limb malformations: phocomelia (“seal” limbs), amelia (absence of limbs)
2. Internal organ malformations: heart defects, duodenal stenosis
3. Eye and ear defects

C. Sensitive Period

Sensitive Period: limb morphogenesis (4-5 weeks) 24-36 days of gestation (38-50 days after LNMP). [There is a high rate of malformation in exposed embryos = 50-80%! Only one dose can cause birth defects in the fetus]

D. Mechanism

1. Inhibition of angiogenesis: thalidomide is believed to inhibit basic fibroblast growth factor (bFGF), which is an endothelial cell mitogen and stimulates limb growth. [Fig 8a]

2. Inhibition of tumor necrosis factor (TNF): thalidomide also inhibits TNF production by monocytes/macrophages which can have both anti-inflammatory and immunomodulating effects

RETINOIDS

Natural and synthetic compounds with a chemical structure and functional properties similar to vitamin A are called retinoids. Maternal hypervitaminosis A during pregnancy is teratogenic in several animal species (“retinoid embryopathy”).

A. Clinical Background
1. Isotretinoin (Accutane) is a retinoid indicated for the treatment of severe, cystic acne
2. First marketed in US in 1982
3. Based upon laboratory animal studies, it was labeled as a Category X medicine

B. Pathology
1. craniofacial malformations (e.g. microtia/anotia)
2. congenital heart disease
3. thymic problems
4. CNS malformations (e.g. hydrocephalus)
5. limb abnormalities
6. postnatal neuropsychological problems

C. Sensitive Period - Weeks 3-5

D. Mechanism

Retinoic acid normally binds to nuclear receptors and serves as an upstream regulator of certain HOX genes in normal morphogenesis. Teratogenic effects may be mediated in part by disruptions of the retinoic acid-sensitive HOX genes.


IMAGING TECHNIQUES AS TERATOGENS

IONIZING RADIATION

NOTE: There is no conclusive proof that human congenital anomalies have been caused by diagnostic levels of radiation exposure. However, they are best limited to those situations when other imaging methods (e.g. ultrasound) cannot be used.

A. Exposure Method

1. diagnostic X-rays (X-ray machines, CT)
2. radiation therapy (e.g. for cancer)
3. radioisotopes (nuclear medicine studies)

B. Pathology
The severity of embryonic damage is related to the radiation dose and the stage of embryo/fetal development. High levels of radiation (e.g. from radiation therapy levels) can cause:
1. CNS damage - microcephaly, skull defects, spina bifida
2. Eye problems
3. Mental retardation
4. Cancer development during childhood

C. Sensitive Period
Based upon Japanese survivors of atomic bombs, 8-16 weeks of gestation is a critical period for brain development.

D. Mechanism
1. cell death
2. chromosomal damage

ULTRASONOGRAPHY (ULTRASONIC WAVES)
Ultrasonography is very commonly used for fetal imaging (transvaginal, transabdominal)
and as a procedural guide for needles (e.g. amniocentesis). There is, as yet, no evidence that ultrasound harms fetal tissues.

Front 119

many metabolic and cellular pathways used during development are unique such that teratogenic drugs/chemicals which cause serious birth defects may have few or no side effects in adult patients. So how the heck do we assess for this in drugs BEFORE it becomes a disaster?

Back 119

Preclinical Studies (nonhuman):

In vitro Studies - these include testing the (experimental) drug on cell, tissue, or embryo culture systems; these tests serve as screening tools

In vivo Studies animal experiments can only suggest that similar effects may occur in humans.

* testing is usually done on two animal species, a rodent (e.g. rat) and nonrodent (e.g. rabbit); this is because some drugs (teratogens) may affect certain species but not others (e.g. thalidomide does not adversely affect rat embryos).

* virtually every drug that has since been found to be teratogenic in humans has caused similar teratogenic effects in animals

* there are drugs that have teratogenic effects in animals when administered in high doses that are not teratogenic in humans given clinically relevant doses (usually there is a safety factor of 10 – 100X when extrapolating from animal doses to human doses)

* although animal testing may identify teratogenic effects of a drug, it can be difficult to extrapolate these effects to humans given clinically relevant doses

Clinical Trials - Phase 1, 2 & 3 (human) - investigational new drugs (IND) are tested on human volunteers and patients.

MARKETING PERIOD

Once a drug has been approved by the FDA, then the drug can be prescribed by physicians. Over time, as more patients are treated with the drug, adverse effects not previously detected by testing may begin to surface (e.g. teratogenicity). These adverse drug effects may be reported as: case reports & epidemiologic studies.

NOTE: 51% of FDA-approved drugs exhibit serious side-effects discovered only post-marketing!

Hint 119

THE PHYSICIAN’S ROLE IN PREVENTION

Exposure of Pregnant Women to Drugs

According to a CDC survey in 1987, 90% of pregnant women averaged 3.8 prescription or OTC drugs from 48 different classes of drugs during their pregnancy!

Categorization of Drugs Based Upon Teratogenic Effects

Note that fewer than 30 drugs have been proven to be teratogenic in humans when used in clinically relevant doses. Many commonly used drugs have been shown to be safe following large, well-controlled studies. The FDA has a classification system for approved drugs based upon a hierarchy of estimated fetal risk.

Front 120

For the following methods of screening:
1. imaging
2. maternal serum (e.g. alpha fetoprotein or AFP levels)
3. amniocentesis/cordocentesis & CVS
4. noninvasive procedures

Which one can be used to estimates risk or trisomies? neural tube defects? chromosome abnormalities? Which ones are the most risky?

Back 120

Ultrasound
• Noninvasive procedure with no known adverse effects on development
• Can be used to image the developing embryo and fetus in great detail, allowing visualization of defects in utero
• Can be used to estimate risk of trisomies
• nuchal translucency ultrasound (NTU) measures thickness of nuchal fold at 9-13 weeks gestation.
• 18% of embryos with nuchal fold thicknesses greater that 3 mm have Down syndrome. Increased thickness correlates with increased risk of trisomy 13, 18, or 21.
• Increased thickness reflects lymphedema
• Predictive accuracy 80-90% when performed by a specialized, highly skilled sonographer and interpreted in combination with maternal age and measurement of serum markers [PAPP-A (pregnancy-associated plasma protein-A), free beta hCG].

Maternal serum blood screening/triple screen
• Used to estimate risk of neural tube defects and chromosomal abnormalities
• Performed 13-16 weeks gestation
• Measure alpha-fetoprotein (AFP produced by fetal liver), estriol, and beta hCG (pregnancy hormones)
• high AFP indicates increased risk of neural tube defects
• low AFP and estriol, high beta hCG indicate increased risk of Down syndrome
• low AFP, estriol, & beta hCG indicate increased risk of Edward syndrome (trisomy 18)
• The maternal serum screening test leads to the prenatal diagnosis of about 95% of cases of anencephaly, 85% of cases of serious spina bifida, 65% of cases of Down syndrome (MOD statistics).

Amniocentesis
• Used to diagnose chromosomal abnormalities and mutations
• Performed between 13-16 weeks gestation
• Involves withdrawal of small amount of amniotic fluid, isolation of fetal cells from that fluid, and karyotyping or analysis of a specific gene sequence
• Risk of miscarriage, 1 in 200 to 1 in 400
• Accuracy rate: 99.4-100%

Chorionic villus sampling
• Used to diagnose chromosomal abnormalities and mutations
• Performed between 8-10 weeks gestation
• Involves biopsy of small piece of chorionic villus and karyotyping or analysis of a specific gene sequence
• Risk of miscarriage: 1 in 100
• Risk of truncated digits if performed during week 8 : 1 in 3000 (no evidence of risk after week 8)
• Accuracy rate: 99-100%

Emerging noninvasive sampling
• Use fetal cells in maternal blood steam (~4-6 cell/ mL) or free-floating fetal DNA from ruptured, dead placental cells. This DNA is identified by its methylation profile of certain genes.
• Very preliminary, but promising technique
• Essentially no risk to mother or baby

Hint 120

Treatment

The techniques used in prenatal diagnosis are at present more numerous than therapeutic options, but it is hoped that this imbalance will become less marked – “the fetus as a patient” concept.

1. prenatal - advances are being made in fetal surgery and the in utero correction of birth defects (e.g. diaphragmatic hernia)

NOTE: Incisions made during fetal operations heal without scarring!

2. postnatal

Front 121

What are some causes for low birth weight?

Back 121

The primary risk factor is that development of the placenta is insufficient to meet the demands of the fetus, resulting in malnutrition of the developing fetus. There are numerous contributing factors of both environmental and genetic origin:

Environmental factors such as poor nutrition, maternal tobacco smoking, drug addiction or alcoholism
Severe anaemia (although hydrops may also occur)
Thrombophilia (tendency for thrombosis)
Prolonged pregnancy
Pre-eclampsia
Chromosomal abnormalities
Diabetes Mellitus
Connective Tissue Disease/Disorders (Systemic Lupus Erythematosis), Ehlers-Danlos Syndrome
Damaged or reduced placental tissue due to:
Chronic renal failure
Sickle cell anemia
Phenylketonuria
Infections such as rubella, cytomegalovirus, toxoplasmosis or syphilis
Twins and multiple births.

Front 122

What is so unique about HUMAN sexuality

Back 122

NOT just about reproduction,

aboiut identity, gender roles, closeness, longing.

Front 123

What is the biggest predictor for post partum depression?

Back 123

(major depressive disorder) Depression before the pregnancy (duh)

high levels of anxiety in itself can be an excellent predictor of post partum depression.

Hint 123

Front 124

Yes, there is a lot of crap in the media about how bad anti-depressants/ drugs can be for the baby... but what about untreated depressed?

Back 124

depression can relapse.. POOR SELF CARE--> alcohol/ drug use

WE NEED TO BE VERY THOUGHTFUL ABOUT TREATING DEPRESSED WOMEN DURING PREGNANCIES.

Hint 124

IAlso, bipolar women are at most risk for bipolar relapse

Front 125

Almost 1 in 5 women at an infertility clinic are there because they have an eating disorder... Why is this so interrelated?

Back 125

Front 126

Which is easier to treat for depression: women during pregnancy or women after pregnancy?

Back 126

Women during pregnancy. After pregnancy--> all kinds of crazy sleep cycles, etc. less in moms favor of thinking clearly. We want to get mom well before baby comes.

more risky to just 'grin and bear it' during pregnancy

Front 127

Explain why this person might not be able to smell. How would you treat this patient? Would he still be able to have kids?

Back 127

Kallman’s Syndrome

- LRH neuron fail to migrate
-HYPOgonadotrophic
- testosterone supplements
-

Hint 127

1. Too little sex hormones—eg Kallman’s Syndrome
a. Cause: LRH neurons arise from the olfactory bulb during fetal development, when there is a failure of LRH neuron migrationdysfunctional hypothalamusdysfunctional gonadotropic anterior pituitary↓testosterone production HYPOGONADOTROPIC
b. Symptoms: loss of smell (because of an affected olfactory bulb), female like appearance or softening of traditional male features, infertility
i. Lack of testosterone during fetal development will result in stunted development of the duct system and puberty will result in stunted development of the penis, seminal vesicles, musculature, skeleton and larynx
ii. Low levels of testosterone and FSH will lead to ↓spermatogenesis in the seminiferous tubules leading to infertility
c. Treatments:
i. Testosterone supplements to replace low levels
1. Won’t restore fertility because also need FSH for spermatogenesis
ii. LRH supplements may not work depending on age because gonadotropic cells and/or their cell receptors may have atrophied with the lack of stimulation

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FOR MEDICAL PURPOSES--> young child presents with super early developement. What could cause this, and how are you supposed to treat this

Back 128

PRECOCIOUS PUBERTY

-hypergonadisim
-LRH superantagonist to desensitize anterior pit gonadotrophic hormones until puberty age (natural reset of gonadostat at that age)

Hint 128

2. Too much sex hormones—eg Precocious Puberty
a. Cause: premature output of LRH causing early onset HYPERGONATROPISM
b. Symptoms: early pubertal maturation
i. Increase testosterone levels as those seen at puberty will cause inappropriate male development in infants
c. Treatment:
i. LRH super-agonist (same treatment for Female Precocious Puberty)
1. Will lead to a desensitization of anterior pituitary gonadotropic cells leading to a ↓ in LH, FSH and testosterone to appropriate pre-pubertal levels
2. Once the average age of puberty has been reached, the treatment can be stopped and the body will similarly reset its gonadostat like that seen during puberty

Front 129

VERY HIGH YIELD:: This patient has never had her period ever... but is currently thinking about having kids someday... she comes in to your office with infertility issue, and you see she has an an unusually high level of androgrens pumping through he system. And then you realize her genotype is actually XY. What is going on here? What happened to the Mullerian signals and Wolffian ducts during development? What happened internally vs. externally during her sexual development? What should you tell her?

Back 129

Androgen Resistance/Insensitivity Syndrome

-Because they are genotypically male, the Y chromosome still signals the Wolffian ducts leading to testes development.

-will still carry the anti-Mullerian signal preventing the development of internal female genitalia.

genotypic males (XY) have an absence or non-responsive androgen receptors (including androstendione, testosterone or DHT)—still producing androgens normally, but their body isn’t able to respond to androgens

Hint 129

3. Lack of sex hormone receptors- eg Androgen Resistance/Insensitivity Syndrome (once but no longer called Testicular Feminization)
a. Cause: genotypic males (XY) have an absence or non-responsive androgen receptors (including androstendione, testosterone or DHT)—still producing androgens normally, but their body isn’t able to respond to androgens
b. Symptoms: internal male genitalia but external female appearance (blind-ending vagina pouch); breast development
i. Because they are genotypically male, the Y chromosome still signals the Wolffian ducts leading to testes development, etc. but because there are no testosterone receptors, they will not descend at birth (cryptochordism)
ii. Genotypic males will still carry the anti-Mullerian signal preventing the development of internal female genitalia
iii. Breast development occurs because breast tissue has its own aromatase which will convert the circulating testosterone into estrogen, leading to breast development
c. Treatments: controversial and not limited to hormonal replacement therapies
i. Due to the lack of androgen receptors in the brain, most will identify as female pyschologically
ii. Most will be raised as female, and the realization they are genotypically male can be devastating and daunting—this is where the controversy comes in—do you tell them outright? Do you slowly reveal the information? Or do you “white lie” and say they have an abnormality that can be easily treated with estrogen replacement therapy?
iii. For actual treatments—the undescended tested will be removed (they pose a tumor risk) and if they are interested in remaining as female, estrogen therapy can be given. If they wish to become male, further surgery can be done to restore external male-like genitalia and testosterone therapy.