Phyiso Clinical Notes Flashcards
1
Q
Ectopic Implantation
A
- Implantation somewhere other than the uterine fundus
- Most common site is oviduct (tubal pregnancy) which results in no decidualization and uncontrolled invasion (can rupture the tissues and cause hemorrhage)
2
Q
What are the Sex-Chromosome Disorders?
A
- Turner Syndrome (45 X)
- Klinefelter Syndrome (47 XXY)
3
Q
Turner Syndrome
A
- 45 X
- Monosomy X – egg or sperm randomly forming without an X chromosome
- Features: wide or weblike neck, low-set ears, delayed/slow growth, short stature, cardiac defects
- Ovarian insufficiency/failure
- Amenorrhea (Primary or Secondary)
- Infertility
4
Q
Mosaic Turner Syndrome
A
- X chromosome absent in portion of the cells
- Also called 45 X mosaicism
5
Q
Inherited Turner Syndrome
A
- Extremely rare
- Happens because of a missing part of the X chromosome
6
Q
Klinefelter Syndrome (Seminiferous Tubular Dysgenesis)
A
- 47 XXY
- Can be complete or mosaic
- Typically X inactivation occurs
- Phenotypically male due to presence of Y chromosome; appearance of male at birth
- At puberty, increased levels of gonadotropins fail to induce normal testicular growth and spermatogenesis
- Typically see low levels of androgens and elevated levels of gonadotropins
- Features: hypogonadism (low production of androgens), gynecomastia (overdevelopment of breast tissue in males), tall stature, typically infertile (due to destruction of seminiferous tubules)
7
Q
What are Gonadal Dysgenesis Disorders?
A
- Ovotesticular DSD
- XX Testicular DSD
- XY Gonadal Dysgenesis
8
Q
Ovotesticular DSD
A
- Characterized by the presence of both ovarian and testicular tissue in the same individual – ovotesties present in 2/3 of affected individuals
- Results from altered sex determination where both the medulla and cortex of the indifferent gonads develop
- Phenotype may be male or female but the external genitalia are ambiguous
- Majority of karyotypes are 46 XX; 20% have 46 XX / 46 XY mosaicism; 10% have 46 XY with mutations in SRY or related genes
9
Q
XX Testicular DSD
A
- 46 XX
- Chromatin-positive nuclei
- Occurs when SRY gene is translocated to an X chromosome
- Ovaries present
- Male appearance of external genitalia but some individuals may have ambiguous external genitalia
- Testes are often small
- Individual may have hypospadias
- Features: gynecomastia, infertility due to azoospermia
10
Q
XY Gonadal Dysgenesis
A
- 46 XY
- Inadequate production of testosterone and AMH by the fetal testes
- External and Internal Genitalia are developmentally variable due to varying degrees of development of the paramesonephric ducts
11
Q
Complete XY Gonadal Dysgenesis
A
- Individuals have internal and external structures that appear female and underdeveloped (streak) gonads
- Do not develop secondary sexual characteristics at puberty
12
Q
Virilizing Congenital Adrenal Hyperplasia (CAH)
A
- Comprises a group of autosomal recessive disorders caused by deficient adrenal corticosteroids biosynthesis – majority is due to deficiency in 21-hydroxylase
- Results in reduced negative feedback inhibition of cortisol (gluccocorticoid), and alteration in adrenal mineralcorticoid and androgen secretion
13
Q
21-Hydroxylase Deficiency CAH
A
- Typically occurs in XX
- Defective conversion of 17OHP to 11-deoxycortisol
- Results in reduced cortisol biosynthesis, reduced negative feedback, increased ACTH secretion, and adrenal androgens are produced in excess
- Enhanced ACTH drive to adrenal androgen secretion in utero leads to virilization of affected female
14
Q
Features of 21-Hydroxylase Deficiency CAH in Females
A
Masculinization of external genitalia
- Clitoral hypertrophy
- Partial fusion of the Labia Majora
- Persistent urogenital sinus
- In rare cases, complete clitoral urethra results
15
Q
Adrenogenital Syndrome
A
- Type of 21-Hydroxylase Deficiency CAH
- Correlated with enzymatic deficiencies of cortisol biosynthesis
- In some male infants the first presentation may be related to insufficient aldosterone production, leading to a salt-wasting state that clinically presents as shock from dehydration
16
Q
Androgen Insensitivity Syndrome
A
- 46 XY chromosome
- Results form point mutations in the sequence that codes for the androgen receptor
- Follows X-linked recessive inheritance
- At puberty there is normal development of the breasts and female characteristics
- Menstruation does not occur
17
Q
Androgen Insensitivity Syndrome: External Genitalia
A
- Female
- Vagina usually ends in blind pouch
- Uterus and Uterine Tubes are absent or rudimentary
- Testes are usually in the abdomen, inguinal canals, or labia majora
18
Q
Presentation of Androgen Insensitivity Syndrome at Birth
A
Exhibit some masculinization at birth
- Ambiguous external genitalia
- Enlarged clitoris
- Blind vaginal pouch
- Absence of uterus
- Testes are in inguinal canals or labia majora
19
Q
5-Alpha Reductase Deficiency
A
- 46 XY
- Inability to produce DHT (can’t convert Testosterone into Dihydrotestosterone)
- Normal testes and vas deferens development
- External genitalia appear female or ambiguous (DHT critical for male external genitalia development)
20
Q
Hypospadias
A
- External Urethral Orifice is malpositioned, usually penis is underdeveloped and curved ventrally (chordee)
- Caused by failure of canalization of ectodermal cord (glans penis) and/or failure of fusion of the urethral folds –> incomplete formation of spongy urethra
- Likely due to inadequate production of androgens from fetal testes and/or inadequate receptor sites for androgen hormones
21
Q
Hypospadias: Epispadias
A
- Urethra opens on dorsal surface of the penis, complex with exstrophy of the bladder
- Rare to present as its own malformation
- Results from inadequate ectodermal-mesenchymal interactions during development of the genital tubercle
- Develops more dorsally and when the urogenital membrane ruptures, the urogenital sinus opens on the dorsal surface of the penis
- Urine is expelled at the root of the malformed penis, which is located in the superficial perineal pouch
22
Q
Glanular Hypospadias
A
External urethral orifice is located on the ventral surface of the glans penis
23
Q
Penile Hypospadias
A
External urethral orifice is located on the ventral surface of body of penis
24
Q
Penoscrotal Hypospadias
A
External urethral orifice is located at the junction of the penis and scrotum
25
Perineal Hypospadias
- Labioscrotal folds (swellings) fail to fuse (most severe), and external urethral orifice is located between the unfused halves of the scrotum
- External genitalia are ambiguous
- Persons with perineal hypospadias and crytorchidism may be misdiagnosed with a XY Gonadal Dysgenesis
26
Ageneis of External Genitalia
- Congenital absence of the penis or clitoris (extremely rare)
- Caused by failure of the genital tubercle to develop, urethra usually opens into the perineum near the anus
27
Bifid Penis
- Usually associated with exstrophy of the bladder and may be associated with urinary tract abnormalities and imperforate anus
- Only one corpus cavernosum present in each penis
28
Diphallia (Double Penis)
- Results when two genital tubercles develop
- Each penis has two corpus cavernosum
- Fewer than 100 cases have been reported worldwide
29
Micropenis
- Results from fetal testicular failure
- Commonly associated with hypopituitarism (diminished activity of the anterior lobe of the hypophysis)
- Penis is nearly hidden by suprapubic fat pad
30
What is the most common Disorder of Sex Development (DSD)?
Glanular Hypospadias
31
Uterine Duplications & Vaginal Anomalies
Result from arrests of development of the uterovaginal primordium during 8th week
- Incomplete development of a paramesonephric duct or failure of parts of one or both paramesonephric ducts to develop
- Incomplete fusion of the paramesonephric ducts
- Incomplete canalization of the vaginal plate to form the vagina
32
Examples of Uterine & Uterine Tube Anomalies
- Double Uterus (Uterus Didelphys) with two cervixes
- Bicornuate with two Uterine Horms
- Bicornuate with rudimentary horns
- Septate Uterus
- Unicornuate Uterus with one Lateral Horn
33
Uterine Tube Anomalies
- Rare
- Include hydatid cysts, accessory ostia, complete and segmental absence of the tubes, duplication of a uterine tube, lack of muscular layer, and failure of the tube to canalize
34
Double Uterus (Uterus Didelphys)
- Failure of fusion of the inferior parts of the paramesonephric ducts
- May be associated with double or single vagina
- May appear normal externally but is divided internally by a thin septum
35
Bicornuate Uterus
- Duplication involving the superior part of the body of the uterus
- If growth of one paramesonephric duct is delayed and the duct does not fuse with its pair, a bicornuate uterus with a rudimentary horn (cornu) develops (may not communicate with uterine cavity)
36
Unicornuate Uterus
Develops when one paramesonephric duct fails to develop resulting in a uterus with one uterine tube
37
Absence of Vagina & Uterus
- Results from failure of the sinovaginal bulbs to develop and form the vaginal plate
- Uterus is typically absent because the uterovaginal primordium induces the formation of sinovaginal bulbs
38
Vaginal Atresia
Results from failure of canalization of the vaginal plate
39
Transverse Vaginal Septum
Presence of septum at the junction of the middle-superior thirds of the vagina
40
Imperforate Hymen
Results from failure of the inferior end of the vaginal plate to perforate
41
What is the most common obstructive anomaly?
Imperforate Hymen
42
Cryptorchidism (Hidden Testes)
- Most common anomaly in neonates
- Can be unilateral or bilateral
- Typically located in inguinal canal but can occur anywhere along the usual pathway of descent
- Cause is unknown but androgen deficiency likely an important factor
- If both testes remain within or outside the abdominal cavity they fail to mature resulting in sterility
- If uncorrected it can lead to a significantly higher risk of developing germ cell tumors
43
Ectopic Testes
- Occurs when part of the gubernaculum passes to an atypical location and testis follows it
- Rare
- Interstitial ectopia occurs most frequently (testis located external to the aponeurosis of external oblique muscle)
44
Locations of Ectopic Testes
- Interstitial
- Proximal part of medial thigh
- Dorsal to the penis
- Opposite side (crossed ectopia)
45
Congenital Inguinal Hernia
- Persistent Processus Vaginalis can exist if communication between Tunica Vaginalis and peritoneal cavity fails to close --> loop of intestine may herniate
- More common in males, especially with undescended or ectopic testis, and in AIS
46
Hydrocele
- Abdominal end of the Processus Vaginalis remains open but too small to permit intestinal herniation
- Peritoneal passes into the Patent Processus Vaginalis resulting in Scrotal Hydrocele
47
If middle portion of Processus Vaginalis remains open, fluid may accumulate result in:
Hydrocele of the Spermatic Cord
48
What is the most common anomaly in neonates?
Cryptorchidism (Hidden Testes)
49
Polyhydramnios
- Excessive amniotic fluid; too much produced or not enough removed effectively
- Results from: GI obstruction (esophageal or duodenal atresia), craniofacial anomaly, trisomy 18 or 21, DM, hydrops fetalis (see fluid accumulation under skin and sometimes organs)
- Maternal clinical signs: abdominal pain, significant swelling or bloating, breathlessness
- If uterus grows too large then can result in increased risk of PROM
50
Oligohydramnios
- Too little/low amniotic fluid (<400 mL); decreased fluid does not provide enough cushion to fetus and umbilical cord (crushing of fetus by myometrum)
- Maternal clinical signs: placental abnormality, maternal HTN
- Results from: fetal renal agenesis, maternal uteroplacental insufficiency, maternal DM, fetal chromosomal abnormalities
51
Absence of Umbilical Artery
- Occurs when have one umbilical artery instead of the normal two; agenesis or degeneration of one umbilical artery
- Present in 1/100 singletons and 5/100 multiples
- Can be associated with chromosomal and fetal anomalies (20%)
- Can impact perinatal and 3rd stage labor outcomes
- Detected before birth by US
52
Placenta Previa
- Occurs when placenta implants in lower uterine segment or cervix
- Often leads to serious 3rd trimester bleeding
- Most common type of abnormal placentation
- 20% of all cases of bleeding are due to this
- Risk factors: previous placenta previa (60%), history of CS
- Types: Total, Partial, Marginal, Low-lying
53
Placenta Accreta Spectrum (PAS)
- Occurs when the placenta grows too deeply into the wall of the uterus
- Believe uterine remodeling during postoperative scar formation (primarily for CS) and pre-existing uterine pathology play a role in formation of this condition
- Initially suspected on US
- 3 types: Placenta Accreta, Placenta Increta, Placenta Percreta
54
Placenta Accreta
- Partial or complete absence of the decidua
- Villious chorion adheres to the myometrium
55
Placenta Increta
Anchoring villi penetrate into the myometrium
56
Placenta Percreta
Anchoring placental villi penetrate through the myometrium to the uterine serosa or adjacent ligaments
57
Hydatidiform Mole
Replacement of normal chorionic villi by dilated or hydropic (edematous) translucent vesicles -- accumulation of fluid in the villi instead of mesenchyme that establishes capillaries
58
Partial Mole
- Portion of villi are edematous; capillaries can be seen in the villi
- Fetal tissue commonly found
- Results from normal ovum being fertilized with two sperm
- Triploid (69 XXY) or tetraploid (92 XXXY) karyotype
59
Complete Mole
- All/most villi are enlarged, covered with trophoblast invasion
- No fetal tissue
- Can result from fertilization of a blighted ovum (does not contain any maternal DNA or contains only faulty DNA); all DNA is paternal
- Can result from fertilization of ovum by two sperm -- duplication of a single sperm
- Frequent karyotype of 46 XX or 46 XY
60
eInvasive Mole
- Complete mole that penetrates or even perforates the uterine wall (15%)
- Diagnosed by persistent high blood levels of hCG
- Trophoblast deeply invades the uterine wall and can cause hemorrhaging
- Responsive to chemotherapy
61
Gestational Choriocarcinoma
- Highly invasive, metastatic tumor that arises from trophoblast cells
- Very rare
- Observed in about 50% of patients with previous molar pregnancies
- Diagnosed by increasing hCG titer without uterine enlargement
- Treatment with combined chemotherapy agents usually curative
62
Dizygotic (Fraternal) Twins
- Originate from two zygotes
- Two amnions
- Two chorions
- Two placentas
- Normal embryonic development
- Results from ovulation of two different eggs by two different sperm
63
Monozygotic (Maternal Twins)
- Originate from the division of a single zygote, but membranes are dependent upon timing of the division (Splitting in two cell stage vs splitting in early blastocyst vs later splitting
64
Relationships between ____/___ are dependent on how blastocysts implant
Amnions/Chorions
65
Monozygotic Twinning: Splitting at Two Cell Stage
- Twins develop separately as dizygotic twins
- Each twin has their own trophoblast, cytotrophoblast, and syncytiotrophoblast layers
- Implant independently of each other
- Normal embryonic development with individual chorions, placenta, and amnions
66
Monozygotic Twinning: Splitting of Blastocyst into Two Inner Cell Masses (Early Blastocyst)
- Two embryoblasts/ICMs
- One common layer of trophoblasts, cytotrophoblasts, and syncytiotrophoblasts
- Share a single chorion and placenta, but have separate amnions
67
Monozygotic Twinning: Splitting after Formation of the Inner Cell Mass
- Embryos occupy a single amnion
- Initially have single ICM that splits into two
- One common layer of trophoblasts, cytotrophoblasts, and syncytiotrophoblasts -- single decidua basalis
- Common amnion, chorion and placenta
68
Testosterone Deficiency: 2nd-3rd Month of Gestation
Results in varying degrees of ambiguity in the male genitalia
69
Testosterone Deficiency: 3rd Trimester of Pregnancy
Leads to problems in testicular descent (cryptorchidism) along with micropenis
70
Testosterone Deficiency: Around Puberty
- Leads to deficits in the development of secondary sexual characteristics
- Lack of virilization (ex. hypoplasia of testes and accessory genitalia, poor muscle development, sparse body hair, high-pitched voice)
71
Testosterone Deficiency: Post-Puberty
Leads to decrease libido, erectile dysfunction, decreased facial and body hair growth, low energy, and infertility
72
Male Hypogonadism: Kallmann Syndrome
- Genetic disorder
- Occurs when GnRH neurons fail to migrate into the hypothalamus during embryonic development
- Characterized by delayed or absent puberty, and an impaired sense of smell
- Form of hypogonadotropic hypogonadism
- Occurs more often in males
73
Testicular Dysfunction (ex. Klinefelter's Syndrome)
(1) Effect:
(2) Classification:
(1) Decreased Testosterone secretion
(2) Primary Hypogonadism (decreased Testosterone, increased LF and FSH)
74
Effect of Pituitary Dysfunction (ex. tumor):
Decreased LH and FSH secretion
75
Effect of Hypothalamic Dysfunction (ex. Kallman's Syndrome):
Decreased GnRH secretion
76
Leydig Cell Tumors
- Tumors of testes (interstitial cell tumors)
- Produce large amounts of testosterone
- Should be considered if male patient presents with asymmetrical testicular enlargement
77
Leydig Cell Tumors: Children
Children with this type of tumor present with precocious puberty which includes early development of pubic hair, penile and muscular growth beyond what is expected for the child's age
78
Male Pattern Baldness
- DHT is the key androgen involved in the induction and promotion of male androgenetic alopecia
- Could be treated with 5 alpha reductase inhibitors
79
Prostate Cancer Treatment Options
- Androgen receptor antagonists
- Radiotherapy
- Radical Prostatectomy
80
Benign Prostatic Hyperplasia (BPH)
- Classic signs and symptoms: urinary frequency, urinary urgency, nocturia (excessive urination at night), difficulty initiating and maintaining a urinary stream, feeling of postvoid fullness in the bladder, dribbling
- Age and androgens have been implicated in the etiology of this disease (estrogen / androgen imbalance)
- 5 alpha reductase inhibitors reduce prostate volume and results in improved urinary flow rates
81
Type 5 PDE Inhibitors (Viagra)
- Used to treat Erectile Dysfunction
- Work by preventing the degradation of cGMP in the vascular smooth muscle of helicine arteries which then allows dilation of the corpora and adequate blood flow into the penis
82
Destruction of the Internal Urethral Sphincter results in:
Retrograde ejaculation
