Physio / Biochemist

Question 1

Prostaglandin E receptors (EP1-EP4) function

Answer 1

EP2-EP4 act through G alfaS to raise cAMP levels and maintain myometrial cell quiescence but switch to G-Alfa-q/11 ca+-activating pathway during labor
EP1 and EP3 receptors act through G-Alfa-q and G-Alfa-i to augment intracellular Ca+ and contractility

Question 2

bias affects the ability to rapidly eliminate certain

intracellular pathogens during pregnancy by wich mechanism ?

Answer 2

pregnancy is associated with an increase in the CD4+ T cells that secrete Th2-type cytokines—for example
interleukins. Th1-type cytokine production—for example, interferon gamma and interleukin 2—appears to be somewhat suppressed, leading
to a Th2 bias in pregnancy.

Question 3

LH acts mainly on …. cell

Answer 3

LH acts mainly on theca cell

Question 4

FSH acts mainly on …. cell

Answer 4

FSH acts mainly on granulosa cell

Question 5

PRL is synthesized and stored in the pituitary gland in chro-mophobe cells called

Answer 5

lactotrophs

PRL is encoded by its gene (10 kb) on chromosome 6

Question 6

testosterone is converted by the enzyme 5a-reductase to

Answer 6

Dihydrotestosterone (DHT)

Question 7

Definition of hirsutism using Ferriman-Gallway Scoring System

Answer 7

Many investigators define hirsutism as a score > or = 4 to 6 using the modified scoring

Question 8

Human Chorionic Gonadotropin This glycosylated peptide hormone is produced by

Answer 8

the placental syncytiotrophoblast.

Question 9

Steroidogenic enzymes catalyze four basic modifications of the steroid structure. These are:

Answer 9

(1) side-chain cleavage (desmolase reaction), (2) conversion of hydroxyl groups to ketones (dehydrogenase reactions), (3) addition of a hydroxyl group (hydroxylation reaction), and (4) removal or addition of hydrogen to create or reduce a double bond (lyase reaction)

Question 10

Circulating estrogens in the reproductive-aged female include estradiol (E2), estrone (E1), and estriol (E3). Difference?

Answer 10

Estradiol is the primary estrogen produced by the ovary during reproductive years. Levels are derived both from direct synthesis in the granulosa cells of developing follicles and through conversion of the less potent estrone. Estrone, the primary estrogen during menopause, is secreted mainly by the ovary. Estriol, the predominant estrogen during pregnancy is secreted primarily from the placenta. However, both estrone and estriol can be derived from androstenedione in the periphery.

Question 11

The anterior pituitary gland contains five hormone-producing cell types:

Answer 11

(1) gonadotropcs (which produce LH and FSH),
(2) lactotropcs (PRL),
(3) somatotropcs (GH),
(4) thyrotropcs (TSH),
(5) adrcnocorticotropes (ACTH).

Question 12

PRL expression is primarily under inhibitory regulation by dopamine. As a consequence of these regulatory mechanisms, damage to the pituitary stalk results in

Answer 12

hypopituitarism for LH, FSH, GH, ACTH, and TSH, but an associated increase in PRL secretion.

Question 13

Compared with the luteal phase, follicular-phase GnRH pulsatility is characterized by higher pulse frequency and lower amplitude. Higher pulse frequency preferentially stimulates LH, whereas lower frequency favors FSH secretion.

Answer 13

more recent data suggest that kisspeptin neurons may actually drive GnRH pulsatility (Terasawa, 2019). Regardless, GnRH pulse rate and amplitude is modulated by a complex array of neurotransmitters and circulating hormones.

Question 14

Other than dopamine, Prolactin-releasing factors, although less potent, include

Answer 14

TRH, vasopressin, vasoactive intestinal peptide (VIP), endogenous opioids, and acetylcholine.

Question 15

ACTH stimulates glucocorticoid production by the adrenal gland’s zona ——- and androgen production by its zona ——.

Answer 15

ACTH stimulates glucocorticoid production by the adrenal gland’s zona fasciculata and androgen production by its zona reticularis.
CRH secretion is under negative-feedback regulation by circulating cortisol produced in the adrenal gland. In contrast, mineralocorticoid production by the zona glomerulosa is pri-marily regulated by the renin-angiotensin system. As a result, abnormalities in the CRH-ACTH pathway do not result in electrolyte disturbances.

Question 16

Clinically, in women with hypothalamic amenorrhea, CRH levels have been found to be elevated. Elevated levels of CRH inhibit hypothalamic GnRH secretion by direct action and by augmenting central opioid concentrations.

Answer 16

This functional pathway may explain, in part, the association between hypercortisolism and menstrual abnormalities. However, recent work suggests that the link may be substantially more complex and involve multiple neural circuits and transmitters.

Question 17

GH secretion by pituitary somatotropes is stimulated by hypothalamic —— and inhibited by ——.

Answer 17

GH secretion by pituitary somatotropes is stimulated by hypothalamic growth hormone-releasing hormone (GHRH) and inhibited by somatostatin.

Question 18

In the recent study just noted, mean follicular-phase length of – days and mean luteal phase length of — days

Answer 18

In the recent study just noted, mean follicular-phase length of 16.9 days and mean luteal phase length of 12.4 days (Bull, 2019)

Question 19

two-cell theory

Answer 19

Ovarian estrogen biosynthesis requires the combined action of LH and FSH on theca and granulosa cells. This concept is known as two-gonadotropin or the two-cell theory of ovarian steroidogenesis

Question 20

the principal serum estrogen in the postmenopausal women

Answer 20

High LH levels can stimulate production of C19 steroids (mainly androstenedione) in ovarian stromal cells. This ovarian-derived androstenedione and adrenal androgens can be converted by peripheral tissues to (Estrone).
The major site for the conversion of androstenedione to estrone is adipose tissue.

Question 21

FSH and LH secreted from which cell in the anterior pituitary ?

Answer 21

Gonadotroph

LH, FSH, TSH and hCG are heteradimers consisting of a common glycoprotein a-subunit linked to a unique beta -subunit.

Question 22

FSH window means

Answer 22

FSH concentrations need to surpass a distinct level to stimulate ovarian follicle growth.

Question 23

How many hours doss Ovulation happen after LH surge onset ?

Answer 23

34- 36 hrs

From peak LH: 12-24

Question 24

Cholesterol converted to androstenedione by which enzyme ?

Answer 24

Cytochrome cholesterol side-chain cleavage enzyme (P450scc)

Question 25

GnRH precursor is located on chromosome .., the linear ...peptide secreted from ..... of the .....

Answer 25

GnRH precursor is located on chromosome 8, the linear decapeptide secreted from arcuate nucleus of the medial basal hypothalamus.

Question 26

GnRH half life

Answer 26

2-4 min due to rapid cleavage by peptidases.

Question 27

Leuprolide half life

Answer 27

If the doses: 7. 5 mg > 1 month 11. 25 mg > 3 months 45 mg > 6-month

Question 28

The transfer in production of estrogens and progesterone from the ovary to the placenta is often called

Answer 28

luteal-placental shift.

Question 29

Graffian follicle size

Answer 29

2 cm =20mm

Question 30

Ovulation happened after -- hrs from E2 Surge

Answer 30

Ovulation happened after 36 hrs from E2 Surge

Question 31

PGE2 Produce vasodilation

Answer 31

PGF2 alfa Cause vasoconstriction and Dysmenorrhea

Question 32

17α-hydroxylase (converts ----- to -------) and 17,20 lyase (converts ------ to ---).

Answer 32

17α-hydroxylase (converts pregnenolone to 17-hydroxypregnenolone) and 17,20 lyase (converts 17-hydroxypregnenolone to DHEA).

Question 33

The protein subunits of Gap junction channels called ——-

Answer 33

Six connexins form a hemichannel (cannexon) and two connexons (one from each cell) form a Gap junction channel

Question 34

The protein subunits of Gap junction channels called ——-

Answer 34

Six connexins form a hemichannel (cannexon) and two connexons (one from each cell) form a Gap junction channel

Question 35

Contraction associated proteins

Answer 35

- Oxytocin receptor - prostaglandin F receptor - connexin -43

Question 36

It’s a nanopeptide synthesized in the magnocellular neurons of the supraoptic and paraventricular neurons.

Answer 36

Oxytocin

Question 37

Wound may heal through the following ways:

Answer 37

1. Primary intention 2. Delayed Primary intention 3. Secondary intention 4. Skin Graft 5. Flap.

Question 38

P53 is a protein that’s encoded by TP53 gene in humans located on short arm of chromosome number

Answer 38

17

Question 39

The average cycle duration approximates 28 days but ranges from 25 to 32 days, even for a given woman.

Answer 39

The follicular or proliferative phase shows considerable phase-length variation. This contrasts with the luteal or secretory postovulatory phase of the cycle, which is remarkably constant at 12 to 14 days.

Question 40

The human ovary contains ---- oocytes at birth, and approximately ---- follicles are present at puberty onset (Baker, 1963).

Answer 40

The human ovary contains 2 million oocytes at birth, and approximately 400,000 follicles are present at puberty onset (Baker, 1963). These are depleted at a rate of approximately 1000 follicles per month until age 35, when this rate accelerates (Faddy, 1992) Only 400 follicles are normally released during female reproductive life. Therefore, more than 99.9 percent of these undergo atresia through a process of cell death termed apoptosis (Gougeon, 1996; Kaipia, 1997).

Question 41

Follicular development consists of several stages. Primordial follicles undergo gonadotropin-independent recruitment from the resting pool and then progress from primary and secondary follicles to the antral stage. This appears to be controlled by locally produced growth factors. Two members of the transforming growth factor which are .......

Answer 41

growth factor-β family include growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP-15), which regulate granulosa cell proliferation and differentiation as primary follicles grow (Trombly, 2009; Yan, 2001). They also stabilize and expand the cumulus oocyte complex in the oviduct (Hreinsson,2002). These factors are produced by oocytes, suggesting that the early steps in follicular development are, in part, oocyte controlled.

Question 42

selection window

Answer 42

During each ovarian cycle, a group of antral follicles, known as a cohort, begins a phase of semisynchronous growth based on their maturation state during the FSH rise in the late luteal phase of the previous cycle. This FSH increase leading to further follicular development is called the selection window of the ovarian cycle (Macklon, 2001). Only follicles progressing to this stage develop the capacity to produce estrogen.

Question 43

what is the precise predictor of ovulation that can be measured to know the average time of ovulation?

Answer 43

The onset of the gonadotropin surge resulting from increasing estrogen secretion by preovulatory follicles is a relatively precise predictor of ovulation. It occurs 34 to 36 hours before ovum release from the follicle

Question 44

LH secretion peaks -- to -- hours before ovulation and stimulates resumption of meiosis in the ovum and release of the first polar body.

Answer 44

LH secretion peaks 10 to 12 hours before ovulation and stimulates resumption of meiosis in the ovum and release of the first polar body.

Question 45

Ovarian progesterone production peaks at | -- to -- mg/d during the midluteal phase.

Answer 45

Ovarian progesterone production peaks at | 25 to 50 mg/d during the midluteal phase.

Question 46

Endometrial cycle

Answer 46

- proliferative phase | - secretory phase

Question 47

The superficial endometrium termed

Answer 47

Functionalis layer (that shed every menses and reconstructed from deeper basalis layer)

Question 48

The most biologically potent naturally occurring estrogen is

Answer 48

17β-estradiol

Question 49

Endometrial Cycle 2 phases

Answer 49

1- Proliferative Phase | 2- Secretory Phase

Question 50

endometrial histological changes of Proliferative Phase

Answer 50

By the late proliferative phase, the endometrium thickens from both glandular hyperplasia and augmented stromal ground substance, which is edema and proteinaceous material. The loose stroma is especially prominent, and the glands in the functionalis layer are widely separated. This is compared with those of the basalis layer, in which the glands are more crowded and the stroma is denser. At midcycle, as ovulation nears, glandular epithelium becomes taller and pseudostratified. The surface epithelial cells acquire numerous microvilli, which increase epithelial surface area, and develop cilia, which move endometrial secretions during the secretory phase (Ferenczy, 1976).

Question 51

endometrial histological changes of Secretory Phase

Answer 51

By day 17, glycogen accumulates in the basal portion of glandular epithelium, creating subnuclear vacuoles and pseudostratification. These changes likely result from direct progesterone action through receptors expressed in glandular cells (Mote, 2000). On day 18, vacuoles move to the apical portion of the secretory nonciliated cells. By day 19, these cells begin to secrete glycoprotein and mucopolysaccharide contents into the gland lumen (Hafez, 1975). Glandular cell mitosis ceases with secretory activity due to rising progesterone levels, which antagonize the mitotic effects of estrogen. Estradiol action also diminishes because of glandular expression of the type 2 isoform of 17β-hydroxysteroid dehydrogenase. This converts estradiol to the less active estrone (Casey, 1996). On cycle days 21-24, the stroma becomes edematous. Next, on days 22-25, stromal cells surrounding the spiral arterioles begin to enlarge, and stromal mitosis becomes apparent. Days 23- 28 are characterized by predecidual cells, which surround spiral arterioles. Between days 22-25, the secretory-phase endometrium undergoes striking changes associated with predecidual transformation of the upper two thirds of the functionalis layer. The glands exhibit extensive coiling, and luminal secretions become visible. Changes within the endometrium also can mark the so-called implantation window seen on days 20-24. Epithelial surface cells show fewer microvilli and cilia, but luminal protrusions appear on the apical cell surface (Nikas, 2003). These pinopodes help prepare for blastocyst implantation. They also coincide with changes in the surface glycocalyx that allow acceptance of a blastocyst (Aplin, 2003).

Question 52

menstruation onset physiology

Answer 52

With luteolysis and declining luteal progesterone production, events leading to menstruation are initiated (Critchley, 2006; Thiruchelvam, 2013). In the late premenstrual-phase endometrium, the stroma is invaded by neutrophils to create a pseudoinflammatory appearance. These cells infiltrate primarily on the day or two immediately preceding menses onset. The endometrial stromal and epithelial cells produce interleukin-8 (IL-8), a chemotactic–activating factor for neutrophils (Arici, 1993). Similarly, monocyte chemotactic protein-1 (MCP-1) is synthesized by endometrium and promotes monocyte recruitment(Arici, 1995). Leukocyte infiltration is considered key to both endometrial extracellular matrix breakdown and repair of the functionalis layer. With endometrial regression, spiral artery coiling becomes sufficiently severe that resistance to blood flow rises to cause endometrial hypoxia. Resultant stasis is the primary cause of endometrial ischemia and tissue degeneration. Intense spiral artery vasoconstriction precedes menstruation and also serves to limit menstrual blood loss. Prostaglandin (PGF2α) play a key role in this events as Progesterone withdrawal increases expression of cyclooxygenase 2 (COX-2),AKA prostaglandin synthase 2, to synthesize prostaglandins. Withdrawal also lowers expression of 15-hydroxyprostaglandin dehydrogenase (PGDH), which degrades prostaglandins (Casey, 1980, 1989).

Question 53

The term “inflammatory tightrope” | refers to

Answer 53

the ability of macrophages to assume phenotypes that vary from proinflammatory and phagocytic to immunosuppressive and reparative. These are likely relevant to menstruation, in which tissue breakdown and restoration occur simultaneously (Evans, 2012; Maybin, 2015).

Question 54

placental lactogen (hPL), which is produced by which cell type ?

Answer 54

produced only by syncytiotrophoblast.

Question 55

Bladder contraction during voiding (micturating) is mediated via innervation of which of the following pathways? 

Answer 55

Detrusor contraction is via Parasympathetic innervation of pelvic splanchnic nerves (S2‐4).  This also causes relaxation of the internal urethral sphincter Note contraction and relaxation of the external urethral sphincter is under somatic control. 

Question 56

Sodium potassium pump carries which form of transport

Answer 56

Active transport

Question 57

the major estrogen produced by the placenta is

Answer 57

Estriol

Question 58

PT/INR is used to evaluate the ---- and ---- pathways while activated partial thromboplastin time (aPTT), which evaluates the ---- and ---- pathways of coagulation

Answer 58

PT/INR is used to evaluate the extrinsic and common pathways while activated partial thromboplastin time (aPTT), which evaluates the intrinsic and common pathways of coagulation

Question 59

which hypothalamic hormone stimulates the release of prolactin?

Answer 59

Thyrotropin-releasing hormone

Question 60

The normal sequence of pubertal changes in the female is:

Answer 60

Thelarche, adrenarche, Maximal growth velocity, menarche

Question 61

The barr body is:

Answer 61

The condensed nonfunctioning X chromosome

Question 62

Physiological changes during Menstrual cycle

Answer 62

Menstrual phase (days 0 - 5): Estrogen and progestin levels fall in the absence of implantation of a fertilized egg, resulting in breakdown of endometrial stroma Stratum functionalis is shed; spiral arteries constrict to minimize blood loss Proliferative phase (days 6 - 14): Stratum functionalis is regenerated by cells from stratum basalis Primarily driven by increasing estrogen levels Corresponds to follicular phase of cycle in ovary Ends at approximately day 14 when ovulation occurs Secretory phase (days 15 - 28): Stratum functionalis undergoes changes to support implantation in the event of fertilization Glands become convoluted and endometrial cells increase glycogen stores Primarily driven by progestin Corresponds to luteal phase of cycle in ovary Following menopause, the endometrium becomes inactive and may eventually undergo atrophy Pregnancy changes Endometrium retains secretory phenotype and stroma becomes decidualized in response to progestins Myometrium undergoes mechanoadaptation to allow distension and accommodation of developing fetus

Question 63

Microscopic (histologic) description of Endometrium in Proliferative phase

Answer 63

* Cellular blue appearance at low power * Round to tubular glands * Even, regular spacing between glands * Pseudostratified columnar cells in glands * Numerous mitotic figures in glands and stroma

Question 64

Microscopic (histologic) description of Endometrium in Interval phase (Day 16)

Answer 64

* Partially developed subnuclear vacuoles * Mitoses present, but not as numerous as in proliferative phase * Less than 50% of cells in a gland with continuous and well developed subnuclear vacuoles

Question 65

Microscopic (histologic) description of Endometrium in Secretory phase

Answer 65

* Relatively pink appearance at low power * Convoluted, irregularly shaped glands * Single layer of columnar or cuboidal cells in glands

Question 66

Microscopic (histologic) description in Early secretory phase (Day 17 - 19)

Answer 66

Day 17: Continuous and well developed subnuclear vacuoles in > 50% of a gland, rare mitoses Day 18: Sub- and supranuclear vacuoles (piano keys) with nuclei in the center of cell Day 19: Nuclei at base of cell, supranuclear vacuoles, start of luminal secretions

Question 67

Microscopic (histologic) description of Endometrium in Mid secretory phase (Day 20 - 22)

Answer 67

Day 20: Maximal intraluminal secretions, stromal cells with hyperchromatic nuclei and high N:C ratio Day 21: Increased stromal edema Day 22: Peak stromal edema

Question 68

Microscopic (histologic) description Late secretory phase (Day 23 - 27)

Answer 68

Day 23: Predecidua surrounds spiral arterioles Day 24: Predecidua bridges multiple vessels Day 25: Thin band of predecidua beneath endometrial surface Day 26: Thick band of predecidua beneath surface Day 27: Abundant predecidua expanding downward from endometrial surface, increased number of stromal granulocytes

Question 69

Microscopic (histologic) description of Endometrium in Menstrual phase

Answer 69

* Endometrial stromal breakdown: dense round aggregates of stromal cells admixed with inflammatory cells and blood * Papillary syncytial metaplasia is common, thought to be a reparative response

Question 70

Microscopic (histologic) description of Gestational changes to the Endometrium

Answer 70

Decidual change: stroma gains abundant eosinophilic cytoplasm, appears polygonal with distinct cell borders Arias-Stella reaction in glandular cells Nuclear enlargement and hyperchromasia Abundant eosinophilic vacuolated cytoplasm Hobnail appearance with cells protruding into glandular lumen

Question 71

Microscopic (histologic) description of Endometrium in in postmenopausal women 

Answer 71

Atrophy Common in postmenopausal women due to estrogen withdrawal Glands composed of inactive low columnar to cuboidal cells Glands often detached from stroma, forming hairpin structures May have cystic change

Question 72

—— is responsible for of the formation of the internal male genitalia l, while ——- is responsible for the formation of external male Genitalia

Answer 72

1- Testosterone | 2- Dihydrotestosterone

Question 73

somatostatin secreted by:

Answer 73

Delta cells of pancreas

Question 74

Hormone produed by supra optic Nucleus In hypothalamus:

Answer 74

oxytocin

Question 75

The major sources of the TRH that stimulates TSH synthesis and secretion are located in

Answer 75

the arcuate nucleus and the median eminence of the hypothalamus

Question 76

Which hormone stimulate the real release of prolactin in postpartum period?

Answer 76

TRH

Question 77

Coagulation physiological changes in pregnancy

Answer 77

Question 78

hCG can be detected in serum as early as - to - days after the LH surge

Answer 78

hCG can be detected in serum as early as 7 to 9 days after the LH surge

Question 79

two-cell theory of estrogen production

Answer 79

progesterone is first metabolized to androgens by theca cells, and granulosa cells then convert androgens to estrogen.

Question 80

The physiologic event that induces completion of the first meiotic division of the oocyte is the

Answer 80

midcycle luteinizing hormone (LH) surge

Question 81

Criteria for Determining Teratogenicity

Answer 81

Essential Criteria: 1. Careful delineation of clinical cases, particularly if there is a specific defect or syndrome 2. Proof that exposure occurred at a critical time during development 3. Consistent findings by at least two epidemiological studies with: a. exclusion of bias, b. adjustment for confounding variables, c. adequate sample size (power), d. prospective ascertainment if possible, and e. relative risk (RR) of 3.0 or greater, some recommend RR of 6.0 or greater or For a rare environmental exposure associated with a rare defect, at least three reported cases. This is easiest if the defect is severe. Ancillary Criteria: 4. The association is biologically plausible 5. Teratogenicity in experimental animals is important but not essential 6. The agent acts in an unaltered form in an experimental model