Week 2 - "Pregnant At Last" Flashcards
1
Q
What is pregnancy?
Physiology
A
Events that occur from the time of fertilization (conception) until birth
2
Q
What is gestational period?
Physiology
A
Time from las menstrual period until birth (usually 40 weeks (+/- 3) or 280 days)
3
Q
What is conceptus?
Physiology
A
The developing offspring of the pregnant woman
4
Q
What is the embryonic period?
Physiology
A
Time from fertilization through to week 8 –> conceptus is called an embryo
5
Q
What is fetal period?
Physiology
A
Time from week 9 through birth –> conceptus is called a fetus
6
Q
Where does fertilization occur?
Physiology
A
Ampulla
7
Q
How do sperms know where to swim to in order to fertilize the egg cell?
Physiology
A
Every month the egg is released from alternating ovaries; the corona radiata of the egg cell secretes a chemoattractant, sperms have specific olfactory receptors which enable them to “smell” their way to the egg
8
Q
What are the steps of fertilisation? (8)
Physiology
A
- The sperm cell weaves past follicular cells and binds to zona pellucida
- Rise in intracellular calcium inside the sperm cell triggers exocytosis of the acrosome (acrosomal reaction) which contains hydrolytic enzymes
- Hydrolytic enzymes from the acrosome cap are released, the act locally, dissolve the zona pellucida. The whip-like structure of the tail pushes the sperm head toward the oocyte membrane
- Head of sperm lies sideway to oocyte, microvilli on the oocyte surround the sperm head. The two membranes fuse, and the contents of the sperm cell enter the oocyte; the sperm cell membrane remains behind
- A rise in intracellular calcium inside the oocyte triggers the cortical reaction, in which the exocytosis of the granules that previosuly lay immediately beneath the plasma membrane occurs. The enzymes released lead to changes in the zona pellucida proteins, causing the zona pellucida to harden –> preventing polyspermy
- The rise in intracellular calcium inside the oocyte induces the completion of the oocyte’s second meiotic division and the formation of the second polar body
- The head of the sperm enlarges and becomes the male pronucleus
- The male and female pronuclei fuse
9
Q
What triggers the acrosomal recation and the release of the contents of the acrosome?
Physiology
A
The binding of the sperm head to the zona pellucida
10
Q
What is the process to the formation of a zygote.?
Physiology
A
Ovulation –> release of secondary oocyte (ovum)
Fertilization
Cleavage
Morula
Blastocyst
Implantation to the endometrium of the uterus
11
Q
How is the concpetus product (blastocyst) swept towards the uterine cavity?
Physiology
A
With the help of the motile cilia of the oviduct epithelium
12
Q
What is different regarding the mitotic divisions that occur with the zygote (cleavage)?
Physiology
A
The daughetr cells produced through mitosis are half the size of the mother cell so that the zygote does not get stuck in the fallopian tube and lead to an ectopic pregnancy
13
Q
How many mitotic cycles does it take to convert to zygote (cleavage) into a blastocyst?
Physiology
A
4 to 5
14
Q
What is the purpose of inner cell mass of the blastocyst?
Physiology
A
It is destined to become the embryo, located internally
15
Q
What is the purpose of trophoblasts from the blastocyst?
Physiology
A
Form the outer superficial layer of cells, Accomplish implantation and develop into fetal portions of placenta (chorionic sac)
16
Q
What are the two distinct cell populations that arise during the formation of blastocycts?
Physiology
A
Embryoblasts
Trophoblasts
17
Q
In which part of the uterus does implantation usually take place?
Physiology
A
Posterior part of the fundus or body of the uterus
18
Q
What are the stages of implantation? (4)
Physiology
A
- Hatching
- Apposition
- Adhesion
- Invasion
19
Q
What happens during the hatching phase of implantation?
Physiology
A
- Degeneration of zona pellucida from lytic factors of the sperm
20
Q
What happens during the apposition stage of implantation?
Physiology
A
Blastocyst aligns loosely with the endometrial surface, typically overlying the uterine epithelium at a receptive spot.
This stage involves minimal contact, with microvilli on trophoblast cells beginning to interact with the endometrium.
21
Q
What is the position of the blastocyst in regards to the endometrium, how is that important?
Physiology
A
The blastocyst are facing endometrium, this way it is easier for blastocyst to receive nutrients during the first 12 weeks, prior to placent adevelopment, from the thickened endometrium
22
Q
What happens during the adhesion process of implantation?
Physiology
A
The blastocyst firmly attaches to the endometrial lining via molecular interactions between adhesion molecules on trophoblasts and the uterine epithelium.
23
Q
Which structures aid the adhesions process of implantation?
Physiology
A
Integrins, selectins, and cadherins mediate this process.
24
Q
What happens during the invasion stage of implantation? What is the effect of that?
Physiology
A
The trophoblast cells differentiate into syncytiotrophoblasts, which invade the endometrial tissue and remodel maternal spiral arteries.
This creates a blood supply to establish the placenta, allowing nutrient and gas exchange.
25
When is the process of placenta formation completed?
| Physiology
By the beginning of week 12
26
What are the two parts of the placenta?
| Physiology
Maternal; decidua basalis
Fetal; chorion frondosum
27
What is the function of the placenta?
| Physiology
It allows oxyge and nutrients to diffuse from maternal blood to fetal blood, while carbon dioxide and waste products diffuse from the fetal to the maternal blood
28
What is the importance of the placenta?
| Physiology
It has a nursing function towrads the fetus and also an endocrine function
29
What is the nursing function of the placenta?
| Physiology
The fetus requires a supply of nutrients in order to grow, these are initially provided through trophoblastic nutrition from the thickened endometrium and then through placental diffusion
30
What is the endocrine function of the placenta?
| Physiology
Produces estrogens, progesterones, hCG which sustain pregnancy, fetal growth aand eventually, help in labor
31
How does the ratio of estrogen: progesterone change in order to help labor?
| Physiology
Progesterone is higher than estrogen initially when that ratio changes, --> important for labor
32
Is the placenta able to convert progesterones to estrogens?
What happens?
| Physiology
No
33
What is the importance of the sulfated hormones being weak and having a low effect on the fetus?
| Physiology
If androgens were to have an effect on the fetus it could lead to masculization of the emebryo (if female) and other adverse effects
34
What is the maternal role in the hormone synthesis (of androgens) during pregnancy?
| Physiology
Provides LDL cholesterol, the raw material for hormone production.
35
What happens to the LDL cholesterol provided by the mother?
| Physiology
The placenta converts LDL cholesterol into progesterone, which is essential for maintaining the uterine lining and preventing contractions.
36
What is the role of the plcanta when it comes to the hormone synthesis during pregnancy (progesterone)?
| Physiology
The placenta cannot convert progesterone to estrogens, but it passes progesterone to the fetus.
37
What does the fetus do with progesterone during the hormone synthesis during pregnancy?
| Physiology
The fetus produces DHEA-S (a precursor for estrogens), which is transferred to the placenta.
In the placenta, DHEA-S is converted into estradiol, estrone, and estriol (estrogens).
Aromatase and other enzymes in the placenta carry out these conversions.
38
Which organ of the fetus produces DHEA-S?
| Physiology
fetal adrenal glands produce DHEA-S from pregnenolone sulfate
39
How does the fetal liver contribute during the hormone synthesis during pregnancy?
| Physiology
The fetal liver helps modify DHEA-S into intermediates that the placenta can use to produce estriol, the primary estrogen in pregnancy.
40
Which enzyme converts Progenenolone sulfate into DHEA?
| Physiology
17-a hudroxylase
12, 20 Desmolase
41
Which enzymes convert DHEA into estradiol?
| Physiology
3b-HSD
17-b HSD
Aromatase
42
Which enzyme converts DHEA-S to 16-a OH DHEA-S?
| Physiology
16a- hydroxylase
43
Which enzymes convert 16a- OH DHEA into estriol?
| Physiology
3b-HSD
17b- HSD
Aromatase
44
Which hormones are important for fetal growth?
| Physiology
Growth Hormone
T4
Cortisol
Insulin
45
Where is fetal insulin produced? When?
| Physiology
Produced by the fetal pancreas by week 12
46
Which hormone is the most important hormone when it comes to regulating fetal growth?
| Physiology
Fetal insulin
47
What is the effect of growth hormonefrom maternal, placental or fetal origins on fetal growth?
| Physiology
Minimal, little effect
48
What is normal fetal growth like for the first 20 weeks of gestations?
| Physiology
Mainly by cellular hypersplasia
49
What is fetal growth like from week 20 to week 28 of gestation?
| Physiology
Hyperplasia and hypertrophy
50
What is fetal growth like from week 28 onwards of the gestational period?
| Physiology
Hypertrophy with rapid accumulation of fat, muscles and connective tissues
51
When does 90% of featl weight gain occur?
| Physiology
Later half of pregnancy
52
When do all the gross characteristics of all the organs of the fetus begin to develop?
| Physiology
Within 1 month after fertilization
53
When are most of the details of the different organs established?
| Physiology
2 to 3 months after the initial development of the organs
54
What are the organs of the fetus, beyond 4 months like?
| Physiology
Grossly the same as those of the neonate just not functioning
55
When does the heart of the fetus start beating and how?
| Physiology
At around 4 weeks, not fully developed but it has autorhythmic cells that have developed and they have their own pacemakers --> 65b/min
ACtual heart starts beating at around 38 to 40 weeks
56
Where are RBCs formed from week 3 to week 8?
| Physiology
Yolk sac and placenta
57
Where are RBCs formed from week 6 to term?
| Physiology
Fetal liver
58
Where else are RBCs formed from week 10 to week 28?
| Physiology
Spleen
59
WHat is the structure that produces RBCs which develops last? When does it start producing RBCs?
| Physiology
Fetal bone marrow, from week 20 to term
60
Why do the fetal lungs remain deflated through-out the pregnancy?
| Physiology
No breathing occurs during intrauterine life, lungs contain clear fluid, not air
61
Why are repsiratory movemnets inhibited during pregnancy?
| Physiology
To prevent filling of the lungs with fluid and debris from the meconium excreted by the fetus' GIT into the amniotic fluid
62
What is the purpose of small amounts of fluid secreted into the lungs, where is it secreted from?
| Physiology
Secreted by alveolar epithelium up until moment of birth, keeping inly clean fluid in the lungs
63
What is the complication associated with abnormal kidney development or severe impairement of kidney functio during pregnancy?
| Physiology
Issues with the fetus' kidneys gretaly reduces the formation of amniotic fluid (oligohydramnios) which can lead to fetal death
64
When does the renal system for regulating fetal extracellular fluid volume anf electrolyte imbalance fully develop?
| Physiology
Late fetal life and reach full development a few months after birth
65
When does urine excretion form the kidneys of the fetus begin?
| Physiology
Week 13 onwards
66
When are small amounts of meconium formed and excreted during egstational period?
| Physiology
From week 28 till term
67
When does ingetsion and absorption of large quantities of amniotic fluid begin?
| Physiology
From week 20 until term
68
What is meconium composed of?
| Physiology
Partly of residue from swallowed amniotic fluid and partly of mucus, epithelial cells, and other residues of excretory products from GI mucosa and glands
69
What is the main source of energy for the fetus?
| Physiology
Glucose
70
What is the fetus' capability of storing fat and proteins like?
| Physiology
High capability
71
When do calcium and phsophate accumulate during pregnancy?
| Physiology
In the 2nd half due to bone ossification
72
WHy does iron accumulate faster than calcium and phospahte during pregnancy?
| Physiology
Required for RBC production, accumulates mostly in the hemoglpbin and also 1/3 of the liver
73
Which vitamins are necessary for the fetal development and growth?
| Physiology
B, C, D, E and K
74
What do most of the reflexes of the fetus involve?
| Physiology
Spinal cord and brain stem --> 3rd to 4th month
75
WHen do functions and reflexes involving the cerebral cortex occur?
| Physiology
Early stages of development at birth
76
When does myelination of some major tracts of the brain occur?
| Physiology
Becomes complete after about 1 year of postnatal life
77
When are anterior pituitary hormones secreted from the fetus?
| Physiology
begin at week 8 and they are independent of hypothalamic influence
78
When are adrenal medulla hormones secreted from the fetus?
| Physiology
E, NE, T3 and T4 begin at week 10
79
When are posterior pituitary hormones secreted from the fetus?
| Physiology
From week 14 onwards
80
When re hypothalamic hormones secreted fromn the fetus?
| Physiology
From week 13 onwards
81
What does the outer definitive zone of the adrenal cortex of the fetus scerete?
Functions?
| Physiology
Cortisol --> multiple functions during fetal life, including promotion of pancreas and lung maturation, induction of liver enzymes, promotion of intestinal tract cytodifferation, in itiation of labor?
82
What does the deeper fetal zone of the adrenal cortex of the fetus secerte?
| Physiology
DHEA-s and androgenic precursors for estrogen synthesis by the placenta --> only present in the fetus, disappears after birth
83
What is the purpose of fetal gonadal hormones that act during organogenesis?
| Physiology
Control sexual differerentiation
84
When do fetal testes differentiate ?
What happens to Leydig and Sertoli cells?
| Physiology
Between weeks 6 to 8
Leydig start producing testosterone, either autonomously or under hCG regulation
Sertoli cells produce anti-mullerian hormone
85
What does the differentiation of the male external genitalia require?
| Physiology
5a reductase to produce DHT
86
What is labor?
| Physiology
Process by which uterine contraction expel the fetus through the vagina to body exterior
87
Why are there no uterine contractions during pregnancy?
| Physiology
Uterus is quiescent because of progesterone and relaxin
88
What is the timin g of parturition controlled by?
| Physiology
Fetus-derived signals (1)
Endocrine and paracrine factors (2)
Stretching of the uterus (3)
89
Once labor is initiated, how is it sustained?
| Physiology
By a series of positive feedback mechanisms (like oxytocin)
90
What are uterine contractions like?
| Physiology
Involunatry (interstitial cells of Cajal) and for the most part independent of extrauterine control
91
How are uterine smooth muscles interconnected?
| Physiology
Via gap junctions, any change to cells will quickly be transferred to the adjacent cells
92
What type of cells initiate spontaneous depolarizations of uterine smooth msucle?
| Physiology
Myometrial Cajal-like interstitial cells --> gap junctions --> contraction
93
What kind of receptores do uterine smooth muscles contain? What happens to them through-out pregannacy?
| Physiology
Oxytocin and prostaglandin receptors
Their expression increases towards the end of pregnancy --> more receptors --> incraesed contractions
94
What is the factor that INITITAES labor (the main one from the mother)?
| Physiology
Prostaglandins
95
What are other factors that initiate labor (from the mother)?
| Physiology
1. Progesterone withdrawal
2. Role of placental corticotropin-releasing hormone
96
Once labor is initiated, what factors maintain it?
| Physiology
Prodtaglandins and oxytocin
97
What are estrogen and cortisol levels like in mother towards teh end of pregnancy? Why?
| Physiology
High, CRH released from placenta --> ACTH and DHEAS released --> increase in cortisol and estrogen (positive feedback mechanism in embryo)
98
Why is progesterone withdrawl one of the factors initiating labor?
| Physiology
Progesterone usually inhibits uterine contractility, by withdrawing progesterone you stimulate:
1. Gap junctions
2. Oxytocin receptors
3. Prostaglandins
4. More positive resting membrane potential
99
What are the effects of estrogen during labor?
| Physiology
Increase gap junctions, increase prostaglanding receptors, increase oxytocin receptors, cause uterine stretch
100
What are the effects of uterine stretch during labor?
| Physiology
Increase prostaglanding receptors and increase in oxytocin receptors
101
What are the effects of increased cortisol during labor?
| Physiology
Increase in prostaglanding receptors and cervical stretch --> increase in maternal oxytocin
102
Why are PG and oxytocin receptors not uniformally expressed in the uterus?
| Physiology
Differential expression more in the fundus than the cervix, if they were found in teh cervix --> contractions would block the xplusion of the fetus
103
What are the effects of uterine stretch and fetal oxytocin during labor?
| Physiology
Stimulate the uterine decidual cells and fetal membranes to increase PG synthesis and produce Prostaglandings which:
1. Stimulate contraction of uterine smooth muscle
2. Promote formation of gap junctions between uterine smooth msucles
3. Cause softening and thinning and dilation of cervix
104
How does oxytocin sustain labor?
| Physiology
1. Baby moves deeper into mother's birth canal
2. Cervix of uterus is stretched
3. Nerve impluses sent ti hypothalamus
4. Hypothalamus sends impulses to posterior pituitary --> oxytocn
5. Posterior pituitary releases oxytocin to blood --> travels to uterine muscles
6. Uterus responds by contracting more vigorously
7. At birth, cervix stretching lesses and positive feedback is broken
105
What are the stages of labor?
| Physiology
Stage of dilation
Stage of expulsion
Placental stage
106
What is the stage of dilation during pregnancy?
| Physiology
The timr ftom the onset of labot to the complete dilation of the cervix (6 to 12hrs)
107
What happens during the stage of dilation of labor?
| Physiology
Regular contractions of uterus, usually with ruprtueing of amniotic sac and complete dilation of cervix (10cm)
108
What is the stage of expulsion of labor?
| Physiology
The time from complete cervical dilation to delivery of baby (10 minutes to several hours)
109
What is the placental stage of labor?
| Physiology
The time after delivery until the placenta is expelled by powerful uterine contacttions mediated by oxytocin (5 to 30 minutes)
110
What are the contractions like during the placental stage of labor?
| Physiology
Contractions constrict blood vessels that wern torn during delivery --> reduce the likelyhood of hemorrhage
111
What is the histology of a normal adult ovary-like?
| Pathology
Dense ovarian cortex with abundant stroma and a few follicles, developing primary follicles can be seen, and also a cloud of pink, which is the corpus albicans
112
What is the gistology of a developingprimary follicle at high magnification?
| Pathology
Central oocyte and surrounding granulosa cells
113
What is PCOS (Stein-Leventhal syndrome)?
| Pathology
A syndrome with excess secretion of androgenic hormones, persistent anovulation and many sucpasular ovarian cysts
Common cause of infertility
114
What is the epidiomiology of PCOS in women of reproductive age?
| Pathology
5 to 10%
115
What is the clinical scale used to diagnose PCOS?
| Pathology
Rotterdam Scale
116
How does PCOS present?
| Pathology
At least 2 out of 3 from Rotterdam criteria:
1. Oligo and/or anovulation
2. Clinical and/or biochemical signs of hyperandrogenism
3. Polycystic ovaries on US
117
What are the risk factors (precursors) of PCOS?
| Pathology
1. Genetic
2. Obesity
3. Sedentary lifetsyle
4. Intrauterine androgen exposure
118
What is hyperandrogenism?
| Pathology
Exessive production of androgens, high concentration of LH and low concentratiosn of FSH
119
What is the pathogenesis of PCOS? (GnRH &Insulin)
| Pathology
The risk factors can lead to:
1. Increased GnRH pulsatile release
2. Increased LH:FSH ratio (increased LH in theca cells)
3. Androgen excess
4. Interefrence with development of follicles
5. Anovulation and polycystic ovaries
OR
1. Insulin resistance
2. Hyperinsulinemia
3. Androgen excess (via increased androgenic enzyme & SHBG)
4. Interefrence with development of follicles
5. Anovulation and polycystic ovaries
120
What are the effects of anovulation?
| Pathology
Occurs because there is no corpus luteum, can lead to:
1. Anovulatory bleed & orregular menstruation
2. Decreased progesterone, unopposed increased estrogen --> risk fo endometrial cancer
3. SUbfertility (impaired oocyte devlopment, high rate of miscarriage
121
What are the clinical presentations of insulin resistance?
| Pathology
Acanthosis nigricans
122
What are the clinical presentations of androgen excess?
| Pathology
Hirsuitism
Acne
Alopecia
123
What is the rate limiting enzyme of androgen biosynthesis?
| Pathology
17 a hydroxylase
124
What do excess ovarian androgens act locally to cause in the case of PCOS?
| Pathology
1. Premture follicular artesia
2. Multiple follicular cysts
3. Presistent anovulatory state
125
What are the serum levels like in patients affected by PCOS?
| Pathology
High serum levels of androgens, lik etestosterone, androstenedione, and DHEAS
126
What happens to the excess androgens?
| Pathology
Excess androgens are converted to etsrogens in peripheral adipose tissue --> exaggerates obesity
127
WHat is the mechanism of isnulin resistance due to in cases of PCOS?
| Pathology
Post-insulin recptor defect, possibly related to decreased expression of a GLUT
128
What are the gross fetaures of PCOS?
| Pathology
Both ovaries are enlarged
Grey-white with smooth surface
129
What is the morphology of the ovaries in patients with PCOS on cut surface?
| Pathology
Cortex of ovaries: thickened, numerous subcortical cysts
130
What is the microscopical appearance of the ovaries in cases of PCOS?
| Pathology
1. Multiple follicles in early stages of development
2. Follicular artesia
3. Increased stroma, occasionally with luteinized cells (hyperthecosis)
4. Morphological signs of absence of ovulation
131
What are the morphological signs that would indicate an abscense of ovulation?
| Pathology
Thick, smooth capsule and abscense of corpora lutea and corpora albicantiae
132
What are the clinical features of PCOS?
| Pathology
1. Menstrual abnormalities
2. Fertility problems
3. Hirsuitism --> usually on face, chest, back or buttocks
4. Weight gain
5. Thinning of hair and hair loss from the scalp
6. OIly skin or acne
7. Acanthosis nigricans: indications of insulin resistance
133
What kind of menstrual abnormalities can be present in PCOS?
| Pathology
Oligomenorrhea (menstrual bleeding that occurs at intervals of more than 35 days)
Secondary amenorrhea (an absence of menstruation for 6 months) or irregular periods
134
What is acanthosis nigricans?
| Pathology
Diffuse, velvety thiockening anf hyperpigmentation of the skin
135
How does PCOS appear on imaging?
| Pathology
Ovarian volume > 10ml
20 or more follicles, 2 to 9mm in diameter
Echodense stroma
136
What is the most common type of cystic lesion?
| Pathology
Follicle cysts
137
How do follicle cysts present?
| Pathology
Asymptomatic, at any age up to menopause
Associated with hyperestrogenism and endometrial hyperplaisa
138
What are signs of hyperestrogenism?
| Pathology
Abnormal vaginal bleeding or enlarged breatss
139
What is the pathogenesis of follicle cysts?
| Pathology
Arise from ovarian follicles (unruptured graafian follicle) and are probably related to abnormalities in pituitary gonadotropin release
140
What is the morphology of follicle lesions?
| Pathology
Thin-walled fluid filled structures
Lined internally by granulosa cells and externally by theca interna cells
SIngle or multiple and unilateral or bilateral
141
How do follicle cysts appear on imaging?
| Pathology
Thin-walled
Unilocular
142
What are corpus luteum cysts?
| Pathology
Most common pelvic mass within the 1st trimester of pregnancy
May develop physiologically during menstrual cycle
143
What is the pathogenesis of corpus luteum cysts?
| Pathology
Failure of corpus luteum to regress after ovum release
Continued progesterone synthesis by the luteal cyst results in menstrual irregularities
Rupture of a cyst can cause mild hemorrheage into the abdominal cavity
144
What is the morphology of corpus luteum cysts?
| Pathology
Typically unilocular (3 to 5 cm in size) and possesses a yellow wall
The contents of the cyst vary from serosanguinous gluid to clotted blood
145
How do corpus luteum cysts appear on imaging?
| Pathology
Diffusely thick wall
Ring of fire (hig hvasclarity on Doppler US)
146
What are theca lutein cysts commonly associated with?
| Pathology
High levels of gonadotropin which causes hyperplasia of theca interna cells: circulating gonadotropins (pregnancy, hydatidiform mole, choriocarcinoma & exogenous gonadotropin therapy) or physical impediments to ovulation (dense adhesions, cortical fibrosis)
147
What are the symptoms of theca lutein cysts?
| Pathology
Asymptomatic
Assocated with hyperandrogenism
148
How do theca lutein appear on imaging?
| Pathology
Bilateral, enlarged, multicystic ovaries (micky mouse appearance; gross and imaging)
149
What are the two paths that could lead to placental inflammations and infections?
| Pathology
1. Ascending through birth canal
2. hematogenous (transplacental) spread
150
Which type of placental infections are most common?
| Pathology
Ascending from birth canal
Bacterial infections most of the time
151
What type of agents could cause ascending infections of placenta?
| Pathology
Group B Strep
Enterococcus
E. coli
Staph
Mycoplasma
Candida
152
What are ascending infections of the placengta associated with?
| Pathology
Premature rupture of the fetal membranes
153
What is the pathogenesis of the ascneding infections of the placenta?
| Pathology
Upon recahing the uterine cavity, the organism elicit maternal acute inflammatory response, demonstartion ofneutrophilic infiltration in the amnion and chorion
154
What happens if the ascending inflammation of the placenta persists?
| Pathology
the fetus may develop its own acute inflammatory response to the infection: fetal neutrophils migrate into muscular walls of the umbilical vessels --> acute funisitis
and large vessels at the placental surface --> acute chorionic vasculitis
155
How common are hem atogenous infections of the placenta?
| Pathology
uncommon
156
Which structures are affected by hematogenous spread placenta infections?
| Pathology
Affects the villi structures --> villitis
157
What agents can cause hematogenousspread infections of the placenta?
| Pathology
Component of TORCH group:
1. Toxoplasmosis
2. Other (syphilis, TB, listerioisis)
3. Rubella
4. CMV
5. Herpes
158
What are the clinical features of placental infections on the mother?
| Pathology
Intrapartum fever
Pospartum endometritis
Pelvic sepsis with venous thrombosis
159
What are the clinical features of placental infections on the fetus?
| Pathology
Pneumonia after inhalation of infection amiotic fluid
Skin or eye infections from direct contact with organism in the fluid
Neonatal gastritis, enteritis or peritonitis from ingesting infected fluid
160
What is the non-pharmacological management of PCOS?
| Pharmacology
1. Calorie-restricted diet
2. Exercise
3. Lifestyle changes
161
What is the first line pharmcaologcal treatment for PCOS?
| Pharmacology
Contraceptives, either oral or intrauterine
162
What is the most common combination of OCP?
| Pharmacology
Combination of estrogen and progestin
163
What is the aim of OCP as a treatment for PCOS?
| Pharmacology
Aids in management of hyperandrogenesis and menstrual dysfunction
Provides contraception --> prevents ovulation and pregnancy
164
What is the MOA of OCPs?
| Pharmacology
Estrogen: provides negative feedbcak to pituitary and hypothalamus --> decreases LH and FSH production in anterior pituitary, increases the synthesis of SHBG in the liver --> inhibition of ovulation & decraeses in adrogen excess
Progestin: thickens cervical mucus and hampers sperm transport
165
What is the duration of treatment with OCPs like?
| Pharmacology
Treatment of choice especially with hursitism but it requires at least 6 months of use
166
What should be the next step if OCPs on their own are not effective for the treatment of PCOS?
| Pharmacology
Add spironolactone
167
Which OCPs should be avoided because of their increased risk for hirsuitism?
| Pharmacology
Norgestrel and Levonorgestel
168
What are the adverse effects of OCPs?
| Pharmacology
Nausea
Headache
Breast tenderness
Weight gain
Irregular bleeding
Mood changes
Increased risk of venous thromboembolism
169
Why are insulin sensitizers given to PCOS patients?
| Pharmacology
They often present with insulin resistnace and hyperinsulinemia, insulin sensitizers can correct that and thus increase the chances of menstrual cyclicity & ovulation
170
What is MOA of Metformin?
| Pharmacology
It is an insulin sensitizer, it blocks Complex 1 in the mitochondria and decreases the production of ATP and increases the accumulation of AMP.
AMP then activates AMPK which decreases lipolysis, increases beta-oxidation of fatty acids and thus increases insulin sensitivity
171
What percentage of women have restored menses with the help of Metformin?
| Pharmacology
50% of women but its ability to provide endometrial protection is less well-establisshed
172
Why is Metformin not first line treatment?
| Pharmacology
OCPs are superior for regulating menses and lowering androgen levels
173
What are the PK of Metformin?
| Pharmacology
Absorbed well orally
Not bound to serum nor metabolised
Excreted unchanged in urine
174
What are the adverse effects of Metformin?
| Pharmacology
GI disturbances: anorexia, nausea, vomiting, abdominal discomfort & diarrhea
Lactic acidosis
Vitamin B12 deficiency: long term use
175
How can B12 deficiency be a consequence of long term Metformin use?
| Pharmacology
1. Reduced Small Intestinal Absorption of Vitamin B12
2. Impaired Calcium-Dependent Transport of Vitamin B12
3. Changes in Gastric pH and IF Secretion
176
Which drugs can be used for treatment of hirsuitism in patients with PCOS?
| Pharmacology
Spironolactone
Finasteride
177
What is the MOA of Spironolactone?
| Pharmacology
Blocks androen receptors --> preventing testeosterone and DHT to act on hair follicles
Inhibits steroid synthesis
178
What is the MOA of Finasteride?
| Pharmacology
Inhibits 5-a reducatse type which is the enzyme that converts testoestrone into DHT
179
What is hirsuitism?
| Pharmacology
A bothersome hyperandrogenic manifestation of PCOS, it may require at least 6 months of treatment before any imporvements are seen
180
What is Spironolactone?
| Pharmacology
An aldosterone antagonist, K+ sparing diuretic
181
When is spironolactone used as treatment in patients with PCOS?
| Pharmacology
Used for the treatment of hirsuitism as an oral add-on therapy if OCPs are ineffective past 6 months
182
What are the adverse effects of Spironoloactone?
| Pharmacology
Menstrual irregularities
Breast tenderness
GI disturbances
Dizziness
Hyperkalemia (because of DCT action on kidneys)
183
What are the contraindications of Spironolactone?
| Pharmacology
Contraindicated in pregnancy
184
What are the PK of Finasteride?
| Pharmacology
Orally absorbed
Highly protein bound and metabolized in liver
Eliminated via bile and urine
185
What are the adverse effects of Finasteride?
| Pharmacology
Teratogenic --> contrainidcated in pregnancy (lead to serious adverse effects involving the male-fetal genitelia)
186
What are the adverse effects of FInasteride on males?
| Pharmacology
Decreased ejaculate
Decreased libido
Gynecomastia
Oligospermia
187
What is Efornithine (Vaniqa)?
| Pharmacology
FDA-approved prescription cream clinically proven to reduce the growth of unwanted facial fair in women
188
When is Eflornithine effective?
| Pharmacology
After 4 to 8 weeks with twice-a day use, hair will reappear if treatment is stopped
189
What is the MOA of Eflornithine?
| Pharmacology
Inhibits ornithine decarboxylase, which is the enzyme that is essential for hair growth in hair follicles, it slows cell division and retards the rate of hair growth
190
What are the side effects of of Eflornithine?
| Pharmacology
Hypersensitivity reactions
191
What are some non-pharmacological treatments for hisuitism?
| Pharmacology
1. Bleaching
2. Depilatory treatments
3. Methods that remove netire hair follcile
192
What is the first line treatment for acne in patients with PCOS?
| Pharmacology
Benzonyl peroxide
193
What is the MOA of Benzonyl Peroxide?
| Pharmacology
Includes antiseptic effects against P. acnesas well as opening of the pores
194
What are the local adverse effects of Benzonyl peroxide?
| Pharmacology
Dry skin
Peeling
Irrritation
195
WHat are the retinoids and their different examples that can be used as treatment for acne in patients with PCOS?
| Pharmacology
They are all derivatives of vitamin A
1. Tretinoin: 1st generation
2. Adapalene (3rd generation)
196
What is the MOA of retinoids in the treatment of acne?
| Pharmacology
Nucleic retinoic acid receptos: once bound to the receptors, the complex functions as a transcription factor that enhances the initiation of transcription -- influences cellular proliferation, differentiation, immune function, inflammationa and sebum production
197
What are 3rd generation retinoids like?
| Pharmacology
They are less irritating and more effective --> do not affect sebum production --> comedolytic nd anti-inflammatory
198
When should retinoid treatment be stopped in case of pregnancy planning and why?
| Pharmacology
Should be stopped at least a month before trying to conceive due to potential teratogenic effects
199
What is clomiphene citrate?
| Pharmacology
A non-steroidal antagonist of estrogen receptors
200
What is the MOA of clomiphene citrate?
| Pharmacology
Inhibits the negative feebaclk of estrogen on the hypothalamus and anterior pituitary by depleting etsrogen recptors in hypothalamus and pituitary and interfering with the binding
Increases secretion of GnRH and gonadotropin levels
Development and maturation of follicle and corpus luteum --> ovulation and pregnancy
201
What are the inidcations for the use of clomiphene citrate?
| Pharmacology
Treatment of infertility associated with anovulatory cycles
202
What are the pharmacokinetics of clomiphene citrate?
| Pharmacology
Well absorved orally
Boudn to plasma proteins and accumulate in fatty tissues
Long half-life (5 to 7 days)
Excreted primarily in feces and some in urine
203
What is the dosage of clomiphene citrate like?
| Pharmacology
50 mg daily starting from phase 5 of the ovulatory cycle
Couple advised to have sexual intercourse every other day for one week around the time of ovulation
204
What are the adverse risks of clomiphene citrate?
| Pharmacology
Long term use --> increases risk of cancer
Abnormal uterine and vaginal bleeding
Breast tenderness
GI disturbasnces
Visual disturbances
Ovarian enlargement
Increased likelyhood of multiple births
205
What is Letrozole?
| Pharmacology
Non-steroidal, reversible competitive inhibitor of aromatase
206
What is the MOA of Letrozole?
| Pharmacology
Inhibits aromatase:
1. Inhibits conversion of testosterone to estradiol and andostenedione into estrone
2. Decreases negative feedback effect of estrogens and increases FSH levels and follicle development
3. Induction of ovulation
207
When is Letrozole prescribed?
| Pharmacology
Off-label for ovulation induction in patients with regular menses
Taken for 5 days, starting at day 3 to 5 of ovulatory cycle, 50mg daily
208
What are the PK of Letrozole?
| Pharmacology
Orally active
Extensive meatbolism in liver
Excreted in urine
209
What are the adverse effects of Letrozole?
| Pharmacology
Fewer than clomiphene citrate
Dizziness & fatigue
Nausea
Constipation
Hot flushes
Moof changes
Fewer multiple gestations
210
What are examples of gonadotropins?
| Pharmacology
hMG
hCG
FSH
211
What are the indications for gonadotropin therapy?
| Pharmacology
1. ANoculatory women with hypogonadotropic hypogonadism secondary to hypothalamic or pituitary dysfunction
2. In women with PCOS who do not respond to clomiphene
3. hCG is used specifiaclly to trigger ovlation when the follicles are mature
212
What are the risks and adverse effects of gonadotropin therapy?
| Pharmacology
Multifetal gestation
Ovarian hyperstimulation syndrome
213
WHat is ovarian hyperstimulation syndrome?
| Pharmacology
Excessive ovarian response, leading to vascular leakage and fluid accumulation in body cavities.
Symptoms: abdominal pain, nausea, vomitingm diarrhea, dyspnea, oliguria, enlarged ovaies on US
214
What can OHSS lead to?
| Pharmacology
Hypovolemia
ELectrolyte imbalances
Acute respiratory distress syndrome
Thromboembolic events
Hepatic dysfunctions
215
What is the MOA of pulsatile GnRH?
| Pharmacology
Pulsatile administration of GnRH
Stimulation of production of FSH and LH, maintains normla feedback mechnaisms and most cycles result in a single dominant follicle
216
What are the chnaces of multifollicular development and ovarian hyperstimulation with pulsatile GnRH?
| Pharmacology
Low
217
What are the indications of pulsatile GnRH treatment?
| Pharmacology
Women with hypogonadotropic hypogonadism who have normal pituitary function
218
219
220
What are the PK of pulsatile GnRH treatment?
| Pharmacology
IV and subQ, IV is preferred
221
What are the adverse effects of pulsatile GnRH treatment?
| Pharmacology
Pain, skin reactions and swellings
222
What are examples of dopamine agonists?
| Pharmacology
Bromocriptine
Cabergoline
Quinagolide
222
What is the MOA of Dopamine agonists?
| Pharmacology
ACtivation of D2 dopamine receptors
Suppression of PRL --> relieve of inhibitory effect of hyperprolactinemia on ovulation
223
What are dopamine agonists?
| Pharmacology
Semisynthetic ergot alkaloids
224
What are the effects of dopamine agonists in patients with prolactinomas?
| Pharmacology
Decrease the size of tumors in more than 50% of patients
225
What are the PK of dopamine agonists?
| Pharmacology
Well absorbed orally, extensive first-pass metabolism
SHort elimination half-life
May be administered vaginally --> less GI effects
226
What are the adverse effects of dopamine agonists?
| Pharmacology
Nausea, vomiting, headache and postural hypotension particularly on initial use
Less frequent: nasal congestion, digital vasospasm, CNS effects (psychosis, hallucinations, nightmares and insomnia)
227
Why do adverse effects of dopamine agonists mainly present upon initial use?
| Pharmacology
Patients then gain tolerance to adverse effects
228
What is oxytocin?
| Pharmacology
Nanopeptide jormone which is normally produced by the hypothalamus and released by the posterior pituitary to induce uterine contractions and lactation
229
What is the signaling for oxytocin?
| Pharmacology
G-protein coupling receptor, coupled to Gaq --> linked to increase IP3, Ca2+ and PKC activation --> contraction
230
What is the MOA of oxytocin?
| Pharmacology
Distention of uterus & stretching of cervix during delivery which causes increase in oxytocin release --> positive feedback, more uterus contractions
231
How is oxytocin administered?
| Pharmacology
Intravenous infusion
232
What are the PK of oxytocin?
| Pharmacology
Inactivated in the liver and kidneys by circulating placental oxycitocinase
233
What are the adverse effects of oxytocin?
| Pharmacology
Induce dose-related hypotension, due to vasodilation with associated reflex tachacrdia
Water retention
Uterine overstimulation
Can cause labor to progress too quickly, causing stronger and proloned contractions
234
What can uterine overstimulation lead to?
| Pharmacology
Trauma of the mother or the fetus due to forfced passagae through an incompletely dilated cervix, uetrine rupture and compromised fetal oxygenation due to decraesed perfusion
235
What is the purpose of prostaglandins in inducing labor?
| Pharmacology
Promote ripening and dilation of the cervix
236
How are prostaglandins administered?
| Pharmacology
Locally (vaginally or intracervically)
237
What is the MOA of prostaglandins?
| Pharmacology
Act on the cervix to enable ripening by modyfying extracellular matrix, relax cervical SM to faciliate dilation and increase intracellular calcium levels --> contraction of myometrial muscle to induce labor
238
What is Dinoprostone?
| Pharmacology
PGE2 analog
239
What are the contrainidcations of Dinoprostone?
| Pharmacology
SHould nit be used in women with a history of asthma, glaucoma or MI
240
What is the major side effect of Dinoprostone?
| Pharmacology
Uterine hyperstimualtion, may be reversed more rapidly using vaginal insert
241
What is Misoprostol?
| Pharmacology
Orally active synthetic PGE 1 analog that can be given for cervical ripening (off-label)
242
What is the normal purpose of Misoprostol?
| Pharmacology
NSAID- induced peptic ulcer
243
What are the adverse effects of Misoprostol?
| Pharmacology
Hyperstimulation
Abortion
244
When should Misoprostol be stopped?
| Pharmacology
At least 3 hours prior to oxytocin therapy
245
What is the aim of tocolytic drugs?
| Pharmacology
Suppress uterine contractions and prolong/delay gestation in pregnant women
246
What are examples of tocolytic drugs?
| Pharmacology
NSAIDs
CA2+ channel blockers
b-adrenergioc agonists
247
What is the MOA of tocolytic drugs (β2-Agonists)?
| Pharmacology
Activate β2-receptors → ↑ cAMP → relaxes smooth muscle in the uterus
248
What is the MOA of tocolytic drugs (Calcium Channel Blockers (CCBs))?
| Pharmacology
Block L-type calcium channels → ↓ intracellular Ca²⁺ → prevents myometrial contractions
249
What is the MOA of tocolytic drugs (NSAIDs)?
| Pharmacology
nhibit cyclooxygenase (COX) → ↓ prostaglandins (PGs) → prevents uterine contractions
250
What is the MOA of tocolytic drugs (Oxytocin Receptor Antagonists)?
| Pharmacology
Block oxytocin receptors → prevents calcium-mediated contractions
251
What is the MOA of tocolytic drugs (Magnesium Sulfate)?
| Pharmacology
Competes with Ca²⁺ at voltage-gated channels → prevents uterine contraction
251
What is PCOS?
| Genetics
Multifactorial disorder that emphasizes the interplay between genes, environment and lifestyle
252
What is the triangle of PCOS?
| Genetics
Androge excess (due to over-active theca cells)
Ovulatory dysfunction
Polycystic ovaries (more than 20 cysts in each ovary --> no follicles)
253
What is the inheritance of PCOS like?
| Genetics
It does not follow a Mendelian pattern (not caused by one single gene) but instead it is considered a complex genetic disorder
254
What factors influenec the inheritance of PCOS that makes it a complex genetic disorder?
| Genetics
Multiple genetic and environmental factors (including epigenetic factors which remain silent until prvoked)
255
What are the potential genetic targets for PCOS? (4)
| Genetics
1. Androgen production: CYP11A1, LHCGR and AR --> androgen synthesis and sensitivity
2. Insulin signaling: INSR and IRS1 --> insulin resistance
3. Gonadotropin regulation: FSHR --> ovulatory dysfunction
4. Energy regulation: PPARG, FTO
256
What is the effect of hyperactive theca cells in PCOS?
| Genetics
Hyperactive theca cells lead to increased androgen production
257
Which genes are affected in androgen production in PCOS?
| Genetics
CYP11A1, CYP17A1, HSD17B --> enhance androgen synthesis
LHCGR --> increased ovarian sensitivity to LH
HSD17B and AR --> alteration of androgen metabolism & receptor sensitivity
258
Where are steroid hormones derived from?
| Genetics
Cholesterol
259
What are the importnat enzymes in steroidgenesis?
| Genetics
17a hydroxylase (converts pregenolone which is a steroidal hormone precursor into 17a-hydro progenolone)
Aromatase (adds the aromatic ring to convert testosterone into estrogen)
260
What is the purpose of the CYP11A1 gene?
| Genetics
Encodes the cholesterol siude-chain cleavage enzyme (which the first rate-limiting step in the production of steroids) which breaks down cholesterol into pregenolone
261
What is the purpose of CYP17A1?
| Genetics
Role in 2 pathways:
1. pregenolone --> 17 OH pregenolone
2. 17 OH pregenolone --> DHEA
262
What is the purpose of HSD17B?
| Genetics
Involved in the the transformation from a weak steroid testosterone to a robust testosterone
263
What is SNP?
| Genetics
SIngle nucleotide polymorphism, occurs at any region of the gene (like the enhancer, inhibitor or promotor)
264
What does a mutation in the SNP of HSD17B lead to?
| Genetics
Increased androgen synthesis
265
What is the role of CYP11A in PCOS?
| Genetics
Variants in CYP11A may lead to increased androgen production by the ovaries, overexpression of the cholesterol side-chain cleavage enzyme has been associated with hyperandrogenism
266
What do polymorphisms of the CYP11A gene lead to?
| Genetics
Polymorphisms, such as promotor region of CYP11A, may incraese enzyme activity --> excess androgen synthesis
267
What is the role of CYP17A1 in PCOS?
| Genetics
Genetic variants in CYP17A, especially in the promoter region, can increase enzyme expression and activity, leading to enhanced androgen production and elevated DHEA
268
What is the role of HSD17B in PCOS?
| Genetics
Dysregulation of HSD17B5 has been linked to increased production of bioactive testosterone in PCOS patients
269
What can variants in the HSD17B gene lead to?
| Genetics
May contribute to elevated testosterone levels and associated symptoms such as hirsutism and acne
270
What is the function of CYP19A1?
| Genetics
Encodes the enzyme aromatase, which converts androgens into estrogens
271
What is the role of CYP19A1 in PCOS?
| Genetics
Decreased expression of the gene --> decreased aromatase --> decreased conversion of testosterone into estrogen --> buildup of androgens
Reduced aromatase activity in PCOS has been noted, particularly in granulosa cells of the ovaries
272
What is the role of LHCGR gene?
| Genetics
Encodes the receptor for LH, which stimulates theca cells in the ovaries to produce androgens
273
What is the role of LHCGR in PCOS?
| Genetics
Increased sensitivity or overexpression of the LHCGR gene can enhance ovarian theca cells responsiveness to LH --.> excessive androgen production
274
What is the effect of SNPs or small insertions/deletions in the promoter region of the LHCGR gene?
| Genetics
It can enhance binding affinity for transcription factors or cofactors
275
What is hypomethylation and what is its effect on the promoter region of LHCGR gene?
| Genetics
Reduced methylation, there is nothing wrong in the DNA sequence but there is a change in the DNA structure, there is a lack of a methyl group which affects the affinity of the chromosome wrapping around the histone
It will leads to an increase in gene expression
276
What is STAR?
| Genetics
Steroidogenic Acute Regulatory Protein
277
What is the function of STAR?
| Genetics
Encodes a protein crucial for transporting cholesterol into mitochondria where it serves as the substrate for steroid hormone synthesis
278
What is the role of STAR in PCOS?
| Genetics
Variations or upregulation in STAR may contribute to increased androgen synthesis by ensuring an abundant cholesterol supply for steroidogenesis (both genetic and epigenetic alterations)
Enhanced STAR activity has been noted in patients with PCOS
279
What is the function of Androgen Receptor (AR) gene?
| Genetics
Encodes the androgen receptor, which mediates the biological effects of androgens by binding to them and regulating gene expression
280
What is the role of AR in PCOS?
| Genetics
Polymorphisms in the AR gene, such as differences in the length of CAG repeats, can alter receptor sensitivity to androgens
281
What does short CAG in the AR gene indicate?
| Genetics
High tenascription activity, whilst long CAG inhibits transcription
282
What is the effect of increased sensitivity to androgns in teh case of AR polymorphism in PCOS patients?
| Genetics
Amplify effects of hyperandrogenism, exacerbating symptoms like hirsuitism and acne
283
What is FST?
| Genetics
Follistatin, inhibits activin, which is a protein that regulates FSH. This indirectly impacts androgen production by affecting ovarian follicle development
284
What is the role of FST in PCOS?
| Genetics
Dysregulation of FST can enhance theca cells activity, leading to excessive androgen synthesis
285
What are the genes involved in insulin signaling?
| Genetics
INSR and IRS1 play a role im insulin resistance which is a common fetaure in PCOS patients
286
What is the mechanism of dysfunction of the insulin signaling pathway in patients with PCOS?
1. Altered insulin metabolism → High insulin levels (hyperinsulinemia).
2. Defects in insulin receptor substrate (IRS1) impair signal transduction, reducing insulin sensitivity.
3. IRS acts as an adapter protein, transmitting signals from the insulin receptor to intracellular pathways.
287
How does insulin resistance affect PCOS?
| Genetics
High insulin stimulates excess androgen production by stimulating ovarian theca cells
288
What is the function of the insulin receptor gene?
| Genetics
Encodes the insulin receptor, a key protein involved in insulin signaling.
289
What is the role of the isnulin receptor in the insulin signaling pathway?
| Genetics
The receptor binds insulin and initiates intracellular signaling pathways that regulate glucose uptake and metabolism
290
What is the role of INSR gene in PCOS?
| Genetics
Variants in INSR can reduce receptor sensitivity to insulin --> insulin resistance --> hyperinsulinemia which stimulates theca cells to produce excess androgens
291
What is the function of IRS1 and IRS 2 genes?
| Genetics
Encode adaptor proteins that mediate insulin receptor signaling by transmitting signals to downstream pathways such as PI3K-AKT and MAPK
292
What is the role of IRS1 and IRS2 genes in PCOS?
| Genetics
Mutations or polymorphisms in IRS1 and IRS2 impair the downstream signaling, reducing glucose uptake and increasing insulin resistance
293
What is the function of AKT2 gene?
| Genetics
Encodes a serine/threonine kinase involved in the PI3K-AKT pathway, which is a critical mediator of insulin signaling that regulates glucose uptake via GLUT4
294
What is the role of AKT2 gene in PCOS?
| Genetics
Dysfunction in AKT2 impairs glucose transport and contributes to insulin resistance --> excerbates hyperinsulinemia
295
What are the genes involved in energy regulator which results in obesity of PCOS patients?
| Genetics
PPAR-γ
FTO
296
What is the function of the PPAR-γ gene?
| Genetics
Encodes a nuclear receptor involved in lipid and glucose metabolism and insulin sensitivity
297
What is the role of PPAR-γ gene in PCOS?
| Genetics
Polymorphisms in the gene are associated with insulin resistance in PCOS
Dysfunctional PPAR-γ impairs the lipid metabolism, promoting adiposity and systemic insulin resistance
298
Which drugs is PPAR-γ a target for and why?
| Genetics
Thiazolidinediones, which are drugs used to improve insulin sensitivity
299
What is the function of SHBG?
| Genetics
Encodes a protein that bends to sex hormones, including androgens and estrogens --> regulating their bioavailability
300
What is the role of SHBG in PCOS?
| Genetics
Insulin suppresses SHBG production --> increased free androgens in circulation
Variants in the SHBG --> reduced SHBG --> hyperndrogenism
301
What are the genes involved in gonadotropin synthesis?
| Genetics
GNRH1
GNRHR
LHB
FSHB
302
What is the role of gonadotropins?
| Genetics
LH and FSH play crucial roles in regulating ovarian function, including follicular development and steroidgenesis
303
What happens to the LH:FSH ratio in cases of PCOS?
| Genetics
Increased LH:FSH ratio and impaired follicular maturation
304
What is the role of the genes involved in gonadotropin synthesis?
| Genetics
Influence the LH: FSH balance
305
What is the function of GNRH1?
| Genetics
Encodes GnRH whoch is the hypothalamus hormone that stimulates the release of LH and FSH from the pituitary
306
What is the role of GNRH1 in PCOS?
| Genetics
Dysregulation of GnRH expression or activity leads to altered GnRH pulse dynamics --> increased LH secretion --> creating an imbalance that produces hyperandrogenism and follicular arrest
307
What are the genes associated with regulation of gonadotropun signaling?
| Genetics
LHCGR
FSHR
GNRHR
308
What can alteration of the gonadotropin signaling genes lead to?
| Genetics
Shift hormonal miliey towards hyperandrogenism and anovulation
309
What is the function of LHCGR?
| Genetics
Encodes for the receptor for LH, expressed on ovarian theca cells. LH binding stimulates androgen production, which is crucial for normal follicular development and ovulation
310
What is the role of LHCGR in PCOS?
| Genetics
Variants in LHCGR can lead to increased sensitivity for LH receptor --> heightened ovarian response to LH --> excess androgne production
311
What is the function of GNRHR?
| Genetics
Encodes the receptor for GnRH which regulates the secretion of LH and FSH from the pituitary
312
What is the role of GNRHR in PCOS?
| Genetics
Variants in GNRHR may affect the frequency and amplitude of GnRH pulses --> increaseed pulses of GnRH favour LH secretions over FSH --> elevated LH:FSH ratio
313
What is the function of FSHR?
| Genetics
Encodes the receptors for FSH, which is expressed on ovarian granulosa cells. FSH signaling is crucial for follicular grgrowth and estradiol production
314
What is the role of FSHR in PCOS?
| Genetics
Variants in FSHR can alter the receptor sensituvity to FSH --> impaired follicular development --> contributes to anovulation and accumulation of immature follicles in the ovaries
315
What are the functions of ESR1 and ESR2 genes?
| Genetics
Encode estrogen receptors that mediate the effects of estrogens on hypothalamus, pituitray and ovaries
316
What is the role of ESR1 and ESR2 in PCOS?
| Genetics
Variants in ESR1 and ESR2 may affect feedback regulation of gonadotropin secretion, contributing to the hormonal imbalances --> impaired estrogen signaling --> exacerbation of LH: FSH imbalance
317
What is the relation between PCOS and ethnicity?
| Genetics
Certain genetic variayions appera more common in specific populations --> variants in DENND1A, THADA, GATA4/NEIL2 genes seen among European and asian populations
318
What in the function of DENND1A?
| Genetics
Not directly involved in adrogen synythesis, this gene influences ovarian theca cell function & androgen production
319
What is the role of DENND1A gene in PCOS?
| Genetics
A splice variant of the gene is overexpressed in the theca cells of women with PCOS --> overexpression is associated with increased androgen production synthesis
320
What are the ligaments of the ovaries?
| Anatomy
Ovarian ligament
Broad ligament
Suspensory ligament
321
Where are the ovaries located?
| Anatomy
Located at the attachment of the broad ligamenr to the pelvuc wall (posteriorly), between the ureter and the external iliac vein
322
Which ligament attaches the ovary to the uretus?
| Anatomy
The ovarian ligament, posterior to the opening of the uterine tube
323
How are the ovaries suspended from the pelvic wall (laterally)?
| Anatomy
Suspensory ligament
324
How are the ovaries suspended from the broad ligament (medially)?
| Anatomy
By the mesovarium
325
What is the mesovarium?
| Anatomy
Part of the ovarian ligament which suspends the ovaries
326
What is the ovarian hilum?
| Anatomy
Point of entry and exit of neurovacsular bundles through suspensory ligament
327
What is the germinal epithelium of the ovaries?
| Anatomy
Layer of peritoneum covering the ovary
328
What is the tunica albuginea of the ovaries?
| Anatomy
Dense connective tissue capsule lying beneath the peritoneum
329
What is the cortex of the ovaries?
| Anatomy
Contain ovarian follicles at different stages of development
330
What is the medulla of the ovaries?
| Anatomy
Contains vessels, lymphatics and nerves
331
What is the blood supply to the ovaries? (arteries)
| Anatomy
Ovarian arteries which arise from the aorta, the reach the ovaries by passing through a fold in the peritoneumm, suspensory ligament
332
What is the venous drainage of the ovaries?
| Anatomy
Pampiform plexus arises from each ovary, unite to form ovarian vein
333
What is the lymph drainage of the ovaries?
| Anatomy
Para-aortic
334
What are the stages of development of follicles?
| Anatomy
1. primordial follicle --> about 2 million at birth, 400 thousand at puberty
2. Primary follicle: 15 to 20 primordial follicles develop into primary follicles monthly
3. Secondary follicles: primary follicles develop into secondary follicles (layer of theca interna and theca externa)
4. Graafian follicle: one secondary follicle develops into Graavian follicle
5. Corpus luteum
6. If fertilized it becomes corpus albicans
335
What are the cortical regions of the ovaries surrounded by?
| Anatomy
Cuboidal cells, surface epithelium, used to be germinal epithelium
336
What is deep to surface epithelium of the ovaries?
| Anatomy
Tunica albiginea
337
What is found in the cortex of the ovaries?
| Anatomy
Primordial follicles which are primary oocytes surroynded by a layer of squamous cells
338
What do primary follicles consist of?
| Anatomy
Primary oocyte surrounded by cuboidal cells
339
What are granulosa?
| Anatomy
Active follicular cells which are composed of several layers of cuboidal cells
340
What is the zona pellucida?
| Anatomy
Glycoprotein secreted by oocyte --> To prevent polyspermy and separate primary oocyte from granulosa cells
341
What is the function of basement membrane?
| Anatomy
Separates follicle and stroma
342
What is the secondary follicle like?
| Anatomy
Primary oocyte surrounded by the zona pellucida and granulosa cells
343
What do fibroblastic cells immediately outside the growing follicle form?
| Anatomy
Steroid-secreting theca interna
Covering of theca externa
344
What are Graafian follciles?
| Anatomy
Mature follicle, might be as large as entire ovary, may be observed as a transparent buldge on the ovary
345
What is PCOS characterized by?
| Anatomy
Enlarged ovaries with numerous cysts, no complete follicular maturation
346
What is the length of fallopian tubes?
| Anatomy
10cm each
347
348
What are the parts of the fallopian tubes?
| Anatomy
1. The funnel shaped infudibulume
2. Finger-like ends called fimbria
3. The ampulla which is the widest portion and it is also the sire of fertilisation
4. Isthmus --> short and narrow portion
5. Intramural --> traverses the uterines wall
349
349
What is the histology of the uterine tubes (fallopian tubes)?
| Anatomy
Folded mucosa
Ciliated cells
Non-ciliated cells
350
What is the funtion of non-ciliated cells in the fallopian tubes?
| Anatomy
Secretory, nutritive and protective
351
What is the uterus?
| Anatomy
Pear shaped hollow organ with thick muscular wall that represents the site of pregnancy
352
What are the different parts of the uterus?
| Anatomy
Fundus --> above the entrance of uterine tubes
Body --> below uterine tubes
Cervix --> narrow lower part, pierces anterior vaginal wall
353
What is the cavity associated withthe cervix?
| Anatomy
Narrow cavity --> cervical cavity
354
How does the cervix communicate with the uterine cavity?
| Anatomy
Internal Os
355
How does the cervix communicate with the vagina?
| Anatomy
External Os
356
What are the relations to the uterus?
| Anatomy
Anterior: uterocervical pouch & superior surface of the blaffer
Posterior: rectouterine pouch (Douglas pouch) & coilds of ileum and sigmoid colon
Lateral: uterine vessels (within broad ligament) & ureters
357
What is the blood supply to the uterus?
| Anatomy
Uterine artery --> branch of the internal iliac artery
358
Where is the uterine artery located?
| Anatomy
Runs medially within the broad ligament, reaches the cervix at right andle & above the ureter
359
What branch does the uterine artery give rise to?
| Anatomy
Small descending branch to the vagina
360
What is the location of the branch to the vagina?
| Anatomy
Ascends up along the lateral wall of teh uterus and inside the broad ligament,
Anastimoses with ovarian artery
361
What are the sexual development features like between male and female in the first 7 weeks?
| Anatomy
No gross morphological differences between male and female embryos
362
During the development of the indifferent gonad where does the gonad appear?
| Anatomy
Appears as an enlargement on the posterior abdominal wall medial to the mesonephros
363
What is the gonadal enlargement referred to?
What is it?
| Anatomy
Gonadal (genital) ridge
Core: intermediate mesoderm
Coelomic epithelium: covering that lines the embryonic body cavity
364
Where are gonads derived from?
| Anatomy
1. Intermediate mesoderm
2. Coelomic epithelium (mesothelium)
3. Primordial germ cells (come from the yolk sac)
365
What are sex cords?
| Anatomy
Extensions of the epithelium that penetrate the mesoderm of the genital ridge
366
Where do primordial germ cells migrate to?
| Anatomy
They migrate towards the genital ridges stimulate further development of the gonad --> oocyte development
367
What do the primordial germ cells give rise?
| Anatomy
Will give rise to oocyte
368
What is a bicornuate uterus?
| Anatomy
Failure of causal paramesonephric ducts to completely fuse, makes pregnancy complicated
