Physio / Biochemist Flashcards

1
Q

Prostaglandin E receptors (EP1-EP4) function

A

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

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2
Q

bias affects the ability to rapidly eliminate certain

intracellular pathogens during pregnancy by wich mechanism ?

A

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.

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3
Q

LH acts mainly on …. cell

A

LH acts mainly on theca cell

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4
Q

FSH acts mainly on …. cell

A

FSH acts mainly on granulosa cell

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5
Q

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

A

lactotrophs

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

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6
Q

testosterone is converted by the enzyme 5a-reductase to

A

Dihydrotestosterone (DHT)

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7
Q

Definition of hirsutism using Ferriman-Gallway Scoring System

A

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

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8
Q

Human Chorionic Gonadotropin This glycosylated peptide hormone is produced by

A

the placental syncytiotrophoblast.

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9
Q

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

A

(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)

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10
Q

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

A

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.

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11
Q

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

A

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

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12
Q

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

A

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

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13
Q

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.

A

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.

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14
Q

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

A

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

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15
Q

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

A

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.

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16
Q

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.

A

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.

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17
Q

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

A

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

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18
Q

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

A

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)

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19
Q

two-cell theory

A

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

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20
Q

the principal serum estrogen in the postmenopausal women

A

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.

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21
Q

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

A

Gonadotroph

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

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22
Q

FSH window means

A

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

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23
Q

How many hours doss Ovulation happen after LH surge onset ?

A

34- 36 hrs

From peak LH: 12-24

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24
Q

Cholesterol converted to androstenedione by which enzyme ?

A

Cytochrome cholesterol side-chain cleavage enzyme (P450scc)

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25
Q

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

A

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

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26
Q

GnRH half life

A

2-4 min

due to rapid cleavage by peptidases.

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27
Q

Leuprolide half life

A

If the doses:

  1. 5 mg > 1 month
  2. 25 mg > 3 months

45 mg > 6-month

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28
Q

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

A

luteal-placental shift.

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29
Q

Graffian follicle size

A

2 cm =20mm

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30
Q

Ovulation happened after – hrs from E2 Surge

A

Ovulation happened after 36 hrs from E2 Surge

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31
Q

PGE2 Produce vasodilation

A

PGF2 alfa Cause vasoconstriction and Dysmenorrhea

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32
Q

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

A

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

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33
Q

The protein subunits of Gap junction channels called ——-

A

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

34
Q

The protein subunits of Gap junction channels called ——-

A

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

35
Q

Contraction associated proteins

A
  • Oxytocin receptor
  • prostaglandin F receptor
  • connexin -43
36
Q

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

A

Oxytocin

37
Q

Wound may heal through the following ways:

A
  1. Primary intention
  2. Delayed Primary intention
  3. Secondary intention
  4. Skin Graft
  5. Flap.
38
Q

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

A

17

39
Q

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

A

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.

40
Q

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

A

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).

41
Q

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 …….

A

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.

42
Q

selection window

A

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.

43
Q

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

A

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

44
Q

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

A

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

45
Q

Ovarian progesterone production peaks at

– to – mg/d during the midluteal phase.

A

Ovarian progesterone production peaks at

25 to 50 mg/d during the midluteal phase.

46
Q

Endometrial cycle

A
  • proliferative phase

- secretory phase

47
Q

The superficial endometrium termed

A

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

48
Q

The most biologically potent naturally occurring estrogen is

A

17β-estradiol

49
Q

Endometrial Cycle 2 phases

A

1- Proliferative Phase

2- Secretory Phase

50
Q

endometrial histological changes of Proliferative Phase

A

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).

51
Q

endometrial histological changes of Secretory Phase

A

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).

52
Q

menstruation onset physiology

A

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).

53
Q

The term “inflammatory tightrope”

refers to

A

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).

54
Q

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

A

produced only by syncytiotrophoblast.

55
Q

Bladdercontractionduringvoiding(micturating)ismediatedviainnervationofwhichofthefollowingpathways?

A

DetrusorcontractionisviaParasympatheticinnervationofpelvicsplanchnicnerves(S2‐4).ThisalsocausesrelaxationoftheinternalurethralsphincterNotecontractionandrelaxationoftheexternalurethralsphincterisundersomaticcontrol.

56
Q

Sodium potassium pump carries which form of transport

A

Active transport

57
Q

the major estrogen produced by the placenta is

A

Estriol

58
Q

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

A

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

59
Q

which hypothalamic hormone stimulates the release of prolactin?

A

Thyrotropin-releasing hormone

60
Q

The normal sequence of pubertal changes in the female is:

A

Thelarche, adrenarche, Maximal growth velocity, menarche

61
Q

The barr body is:

A

The condensed nonfunctioning X chromosome

62
Q

Physiological changes during Menstrual cycle

A

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

63
Q

Microscopic (histologic) description of Endometrium in Proliferative phase

A
  • 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
64
Q

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

A
  • 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
65
Q

Microscopic (histologic) description of Endometrium in Secretory phase

A
  • Relatively pink appearance at low power
  • Convoluted, irregularly shaped glands
  • Single layer of columnar or cuboidal cells in glands
66
Q

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

A

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

67
Q

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

A

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

68
Q

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

A

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

69
Q

Microscopic (histologic) description of Endometrium in Menstrual phase

A
  • 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
70
Q

Microscopic (histologic) description of Gestational changes to the Endometrium

A

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

71
Q

Microscopic (histologic) description of Endometrium in in postmenopausal women

A

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

72
Q

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

A

1- Testosterone

2- Dihydrotestosterone

73
Q

somatostatin secreted by:

A

Delta cells of pancreas

74
Q

Hormone produed by supra optic Nucleus In hypothalamus:

A

oxytocin

75
Q

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

A

the arcuate nucleus and the median eminence of the hypothalamus

76
Q

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

A

TRH

77
Q

Coagulation physiological changes in pregnancy

A
78
Q

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

A

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

79
Q

two-cell theory of estrogen production

A

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

80
Q

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

A

midcycle luteinizing hormone (LH) surge