Week 1 Flashcards
Describe the ovary
Produces gametes and hormone - exocrine and endocrine function
3cm long in young, often smaller in elderly
Surface is scarred and pitted
Ovary blood supply
Ovarian artery, arises from aorta at level of the kidney
Venous drainage of the ovary
Ovarian vein, drains to IVC on right, left renal vein on left
Lymphatics of ovary
drain to aortic nodes at level of renal cells
describe the broad ligament
peritoneal sheet draped over uterus and uterine tubes
ovaries attached to posterior layer by short mesentery (the mesovarium)
describe the ovarian ligament
fibrous cord, links ovary to uterus
describe the suspensory ligament of the ovary
lateral wall of pelvis to ovary
carries ovarian artery and vein
describe the round ligament
connects the uterus to the labia majora
what is the rectouterine pouch
extension of peritoneum into the space between the posterior wall of the uterus and the rectum
what is the uterovesical pouch
fold of the peritoneum over the uterus and bladder
two lowest parts of peritoneum
rectouterine and uterovesical pouches
describe the uterine tubes
in free margin of the broad ligament
about 13cm long
NOT directly connected to ovary
what are the parts of the uterine tubes
infundibulum
ampulla
isthmus
interstitial/uterine part
describe the infundibulum of UT
funnel shaped opening to peritoneal cavity, fringed by finger like FIMBRIAE
describe the ampulla of UT
middle section of uterine tube where fertilisation occurs
describe the isthmus of UT
short narrow section of uterine tubes connected to uterine wall
name the parts of the uterus
Body
Cervix - neck
Fundus - rounded part at the top
Isthmus - narrowing between body and cervix
what is a bicornuate uterus
uterus that hasn’t fused and so has two ‘horns’
regular positioning of the uterus
anteversion and anteflexed
20% show retroflexion and retroversion - no symptoms
blood supply to uterus
uterine artery, branch of internal iliac artery
venous drainage of uterus
uterine vein drains to internal iliac vein
lymphatics of uterus
body - para-aortic nodes
cervix - internal iliac nodes
layers of the scrotum wall
skin
dartos muscle (wrinkly appearance)
external spermatic fascia
cremasteric fascia
internal spermatic fascia
tunica vaginalis
describe the cremaster muscle
skeletal muscle
deep to dermis
runs within spermatic cord
contracts to raise testis in cold weather
- cremasteric reflex
describe the tunica vaginalis
closed sac of peritoneum, visceral and parietal layers
space between containing film of peritoneal fluid
excess fluid in TV = hydrocele
describe the duct system of the testis
ends of a coiled seminiferous tubule join to form a straight tubule
all the straight tubules join to a network ‘rete testis’
from this network, efferent ductules leave and join the epididymis
describe the epididymis
very coiled tube, continuous with ductus deferens
so tightly coiled that it has a gross formv(head, body and tail)
lined by pseudostratified columnar epithelium with stereocilia
- increase area for absorption
- monitor and adjust fluid composition
blood supply of testis
testicular artery
venous drainage of testis
pampiniform plexus (network of veins surrounding testes, cooling arterial blood)
drains to testicular vein then IVC on right
drains to renal vein on left
lymphatics of testes and scrotum
testes to para-aortic nodes
scrotum to inguinal nodes
describe the ductus deferens
45cm long
runs in spermatic cord, through inguinal canal
lies on side-wall of pelvis, turns medially to base of bladder
enlarges at end - ampulla
also attached here to seminal vesicle
describe the seminal vesicles
convoluted tubular glands
5-10cm in length
secretes an alkaline viscous fluid
- contains fructose (used for ATP production by sperm)
- contains prostaglandins which aid sperm mobility and viability
describe the ejaculatory ducts
ducts of seminal vesicle joins with the ductus deferens on each side to form the ejaculatory duct
penetrates the prostate gland, empties into the urethra
describe the prostate gland
surrounds beginning of the urethra
secretes a slightly acidic fluid containing citrate (used by sperm for ATP production), acid phosphatase, proteolytic enzymes (liquify coagulated semen)
passes its secretion to the urethra via many prostatic ducts
describe the bulbourethral glands
pea sized
produce a mucus-like secretion
ducts open to spongy urethra
Why do we not use human embryos when examining histology
Most cadaveric ovaries are post-menopausal and so have different structures. Difficult to get healthy human tissue to section.
What is the site of developing oocytes and follicles
Medulla of the ovary
Describe primordial follicles
First stage of development
One layer of follicular cells around the outside edge
Oocyte in the middle
Describe primary follicles
More than one layer of follicular cells around the outside edge
Pink ring - zona pellucida (glycoprotein coat)
Oocyte in the middle
What is the antrum
Fluid filled space in the middle of a secondary follicle
Describe a secondary follicle
Antrum in centre and Oocyte
Granulosa cells surround oocyte
Theca cells surround granulosa
Theca means shell
Function of theca cells
Produce androgens which are passed to granulosa cells
Function of granulosa cells
Contain an enzyme called aromatase which converts androgens to oestrogens
Describe follicular atresia
Spontaneous degeneration (apoptosis)
Can happen at any stage of life
Hormonally controlled
Granulosa cells die first and so cannot support developing oocyte and follicle dies.
Describe the structure of a pregnant ovary
Once oocyte is ovulated it takes some granulosa cells with it. The rest of the cells re-organise to form corpus luteum structure.
This is an endocrine structure that supports pregnancy by releasing progesterone from fat (foamy cytoplasm)
Describe primordial germ cells
Undergo lots of mitotic. division within the gonads
Cells are diploid
The cells then enter into meiosis to generate haploid gametes capable of fertilisation
What are oogonia
cells that are developed into oocytes.
produced by Primordial germ cells dividing by mitosis. They begin meiosis but only get to the point of prophase 1. where they get arrested.
At this stage the oocyte is called a primary oocyte.
What happens in oogenesis when puberty is hit
Hormonal influences ‘wake up’ the oocytes.
Oocyte completes meiosis 1 to become secondary oocyte. Then arrested again in metaphase 2.
Primary follicles resume development. Grow and develop to help support oocyte. Follicle is getting reading to eject the follicle containing oocyte into reproductive tract.
What is a “polar body”
When the primary oocyte undergoes meiosis 1 it forms two daughter cells.
One secondary oocyte and one ‘first polar body’ containing just nuclear material so that the oocyte can be haploid.
What occurs in oogenesis after fertilisation occurs
Oocyte undergoes meiosis 2 to form polar body and ovum (zygote)
First stage in spermatogenesis
Spermatogonia stem cell undergoes mitosis to form Type A spermatogonia (repopulation) and type B spermatogonia (go on to synthesise sperm)
What happens in spermatogenesis when puberty is hit
Type B spermatogonia undergo mitosis to form primary spermatocytes. These undergo Meiosis 1 and 2 to form 2 secondary spermatocytes and 4 identical spermatids respectively.
Describe spermiogenesis
No further division.
Differentiation to form sperm from circular spermatids.
Acrosome forms surrounding the nuclear material which then condenses and changes shape to form head structure.
Flagellum forms
Midpiece containing mitochondria for energy.
Excess cytoplasm is shed and phagocytosed.
74 days
HWere are mature and immature sperm found ina seminiferous tubule
Mature - Lumen
Immature - Outsides
Describe sertoli cells
Hard to spot, need special staining.
Produce androgen receptor.
Tall columnar cells that extend from BM to lumen.
Provide nutrients, mechanical and hormonal support to developing germ cells. Also involved in phagocytosis and help to create blood-testis barrier.
Cytoplasms connected by tight junctions.
Two compartments of seminiferous tubules
Basal compartment and adluminal compartment.
Immature cells are found in the basal compartment where spermatogonia and early spermatocytes are found.
Describe leydig cells
Large nuclei found at one end of the cell
Develop in clusters
Hormone producing cell, found near capillaries
Produce androgens in the form of testosterone and pass them to sertoli cells.
how many polar bodies are formed in oogenesis
3
What is a necessary cause
One that must be present for the outcome to take place, but can be present without the outcome ocurring
what is a sufficient cause
if the cause is present then the outcome ALWAYS occurs. But the cause isnt required for the outcome.
What is casual inference
Causal inference is a thought process, which help us make sense of data on cause and effect.
In causal inference, we use criteria to carefully appraise and interpret all the evidence available to help us formulate a subjective, value judgement on the likelihood of a causal relationship between an exposure and an outcome.
what is sensitivity in screening tests
how good a test is at correctly identifying people who do have the condition of interest
a/(a+c)
what is specificity in screening tests
how good a test is at correctly identifying people who do not have the condition of interest
d/(b+d)
2 types of receptors
cell surface
Intracellular and interact with lipophilic hormones
Where are hormones metabolised
Liver, and to a lesser extent the kidney
where are steroid hormones synthesised
from cholesterol
process occurs in mitochondria and smooth ER
describe oestrogen
mixture of oestrone and oestradiol
- oestrone secreted from ovary or converted from androstenedione
- oestradiol produced by ovary, through conversion of oestrone (via aromatase)
describe androgens
synthesised in testes (leydig cells), the ovary and the adrenal gland
regulate the development of male primary sex organs, secondary sex characteristics and important in libido and sexual arousal
describe progestogens
synthesised from cholesterol via pregnenolone
produced primarily in corpus luteum, adrenal glands and placenta
- endometrial development
- pregnancy maintenance
- mammary gland development
what are the 3 main sex hormones
progestogens
androgens
oestrogens
role of hypothalamus in menstrual cycle
secretes gonadotropin releasing hormone which stimulates the anterior pituitary to release follicle stimulating hormone and luteinising hormone.
describe hypothalamic control
neurosecretory cells produce GnRH (gonadotrophin releasing hormone)
secreted into portal vessels in pulsatile manner
activates receptor within anterior pituitary
describe the anterior pituitary gland
secretes peptide hormones - gonadotropins
- FSH
- LH
- act on ovary
describe the posterior pituitary
secretes oxytocin
- involved in childbirth and lactation
describe the role of the ovaries in menstrual cycle
levels of FSH and LH trigger follicle maturation and regulate steroid hormones production in the ovary
describe follicle stimulating hormone
initiates recruitment of follicles
supports growth of the follicle, especially the granulosa cells
describe luteinising hormone
supports theca cells
receptors expressed on maturing follicle
LH surge triggers ovulation
describe folliclular phase
characterised by growth of dominant follicle
- progesterone production is low
- oestrogen is rising due to conversion of androgens to oestrogens via aromatase
function of kit-Ligand
signals to stromal cells and recruits them to become theca cells lining the follicle
describe development of the secondaru follicle
FSH secretion increases
LH levels increase
Theca develops - follicle gets independent blood supply
Granulosa cells develop FSH, oestrogen and androgen receptors
describe levels of FSH and LH in development of secondary follicle
LH and FSH synthesis is stimulated but secretion is inhibited
FSH levels decrease. FSH and LH levels diverge as oestradiol inhibits FSH more than LH
Developing follicles produces hormone inhibin which inhibts FSH secretion but not LH
describe feedback in the follicular phase
as oestrogen levels rise they feedback on the hypothalamus to stop producing GnRH and the anterior pituitary to stop producing LH and FSH. However, as oestrogen levels get really high in days 12-14 this triggers positive feedback on the hypothalamus and anterior pituitary, causing a surge in LH and triggering ovulation.
effect of oestrogens on the endometrium
thickening of the stroma
elongation of uterine glands
growth of spiral arteries
describe ovulation
rising oestrogens increase responsiveness to GnRH and its secretion
Oestradiol peaks, progesterone rises
High oestradiol triggers LH secretion by gonadotropes
LH surge
Ovulation occurs
Oestradiol decreases
effects of LH on the follicle and the oocyte
stimulates enzymes that initiate breakdown of the follicle wall and release of mature oocyte.
Also triggers completion of first meiotic division of the oocyte.
describe the luteal phase
formation of corpus luteum, this secretes progesterone and a little oestrogen
progesterone stimulates development of secretory endometrium
LH and FSH levels decrease due to levels of oestradiol, progesterone and inhibin.
oestradiol and progesterone levels decrease late.
What happens if implantation occurs
corpus luteum does not degenerate but remains, supported by human chorionic gonadotropin that is produced by the developing embryo (hCG tested for in pregnancy tests)
what happens if implanatation does not occur
no hCG produced, so the corpus luteum degenerates and the menstrual cycle restarts
what occurs in menstruation
regression of corpus luteum and a reduction in progesterone
leukocyte infiltration of endometrium
constriction and breakdown of spiral arteries - ischaemia
menstruation begins.
3 layers of the uterine wall
Endometrium
Myometrium
Perimetrium
How to identify the endometrium from the myometrium
presence of glands
2 layers of the endometrium
Stratum functionalis
Stratum basalis
Describe the stratum functionalis
Superficial
Thick
Top portions of glands
Temporary, unorganised
Spiral arteries
Shed in menstruation
Describe the stratum basalis
Darker
More cells = more nuclei = darker staining
Straight arteries
Base of glands
Not shed in menstruation
What happens to glands in the secretory stage
Become larger
Secrete a carbohydrate, glycogen rich secretion.
Become coiled/twisting around
What kind of tissue is endometrial stroma
Framework of connective tissue found beneath epithelial lining.
Which layer of the uterine wall is the thickest and why
Myometrium
Allows for strong contractions to expel the foetus during childbirth and the dead endometrial tissue during menstruation
Describe structure of glands in the proliferative stage
Thin and straight
what happens to the corpus luteum after ovulation
it degenerates and becomes a fibrous scar called the corpus albicans
What is the name of the thick connective tissue capsule enclosing the testes
tunica albuginea
what is typical mendelian inheritance
inherited from a single gene
what is incomplete penetrance
it is possible to inherit the genes but not have the condition
what are modifier genetic variants
genes that you inherit alongside the condition that can worsen the condition
examples of AR conditions
spinal muscular atrophy
sickle cell disease
cystic fibrosis
haemochromatosis
congenital adrenal HYPERplasia
Tay-sachs
what are obligate carriers
females who must be carriers based on the affected males in a sex-linked condition.
what are manifesting carriers
due to skewed x inactivation, females are slightly affected by a sex-linked condition
how to spot difference between AD and X-linked D inheritance on pedigree
X-linked Dominance has no male-male transmission
examples of x-linked dominant inheritance
Rickets
Incontinentia pigmenti
Rett syndrome
Describe mitochondrial DNA
made up of little circles, much smaller that dna in nucleus. Only 16.6 kilobase (16,600) pairs. Nuclear genome is 3200 million base pairs.
37 genes
No introns
Inherited only from the mother
syndromes often affect muscle, brain and eyes
what is heteroplasmy
a mix of copies of several chromones in each mitochondrion
what is the threshold effect
condition occurs when a threshold of variant copies is reached
mitochondrial DNA
what is genetic anticipation
when a triplet repeat expansion gets bigger as you go down the generations in the family and so the disease gets worse with each individual. (increasing severity and earlier ag eof onset)
- HD
- fragile X syndrome
- Myotonic dystrophy
what is gonadal mosaicism
mutation in autosomal dominant condition in that the child is affected and the parent isnt.
differences in mutations in proto-oncogenes and tumour-suppressor genes
tumour suppressor genes - loss of function
proto-oncogenes - gain of function
describe sporadic cancer
common
late onset
single primary tumour
describe familiar cancer
uncommon
early onset
often multiple primaries
role of tumour suppressor genes
some inhibit progression through the cell cycle
some propmote apoptosis
some act as DNA repair genes
Example of proto-oncogene
RET
examples of tumour suppressor genes
BRCA1, BRCA2, MLH1, MSH2, APC
what are DNA repair genes
a type of TSGs
act to minimise genetic alterations
Important in some common hereditary cancer predisposition syndromes
- breast/ovarian and colorectal cancer
in what form are most cancer predisposition syndromes inherited
autosomal dominant
mostly due to an inherited altered TSG and then subsequent inactivation of the wild-type gene copy
(two hit hypothesis)
what to look for when diagnosing familial cancer
family history
multiple primary tumours
early age of onset
statistics for how many breast cancer cases are familial
5-10%
what genes are altered most commonly in breast cancer
BRCA1
BRCA2
(male breast cancer suggests BRCA2)
what genes are altered less commonly in breast cancer
TP53
PALB2
PTEN
CDH1
statistics for BRCA1 mutation cancers
approx 72% risk of breast cancer by 80yo
approx 44% risk of ovarian cancer by 80yo
(population risk 10% and 1.5% respectively)
statistics for BRCA2 mutation cancers
Female
- 69% risk of breast cancer by 80
- 17% risk of ovarian cancer by 80
Men
- 4% for breast cancer by 80
- 27-41% for prostate cancer by 80
function of bRCA1 and BRCA2 proteins
DNA repair by homologous recombination of double-strand breaks
pattern of inheritance for familial colon cancer
mostly autosomal dominant
mostly Lynch disease (2-3%)
some: familial adenomatous polyposis, causes 0.5% of CRC
Describe Lycnch syndrome
aka HNPCC (hereditary nonpolyposis colon cancer)
CRC risk of 50-60%
Due to inheritance of mutation in MMR system genes (important for accurate DNA replication)
genes causing HNPCC
MLH1 - 50%
MSH2 - 40%
MSH6 - 7-10%
PMS2 - <5%
describe familial adenomatous polyposis
mutations in the APC gene - chromosome 5
hundreds of polyps form in colon
(can also cause congenital hypertrophy of the retinal pigment epithelium in 80%)
Annual bowel screening from 11yo
describe MYH/MUTYH polyposis
autosomal recessive
like a mild form of FAP
Normal function is the base excision repair gene
high risk of carcinoma when mutated
2 yearly colonoscopy
Describe Li fraumeni syndrome
rare
Autosomal dominant cancer predisposition
- Breast cancer
- Brain tumours
- Sarcoma
- Leukaemia
- Adrenocortical carcinoma
Mutations in master control gene TP53
Chance of cancer: 50% by 30yo, 90% by 50yo
examples of AD conditions
inherited breast, ovarian or colon cancer
APKD
NF1
Huntingtons
what is a consanguineous family
incestous
These families are more likely to display AR inheritance
pedigree pattern for each form of inheritance
AD - vertical
AR - horizontal
XR - knight’s move
XD - similar to Ad, but no male-male transmission
3 forms of atypical inheritance
genetic anticipation
gonadal mosaicism
mitochondrial
what does the ductus deferens develop from
the mesonephric ducts
what are antral follicles
follicles containing an immature egg
what are the 9 bradford hill criteria
strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy.
describe huntington disease
autosomal dominant
onset between 30 and 50
progressive chorea, dementia and psychiatric symptoms
CAG repeat units, expansion of tract to 40+ repeats causes insoluble protein aggregates and neurotoxicity.
No cure
presymptomatic testing
Describe myotonic dystrophy
Autosomal dominant with genetic anticipation
Progressive muscle weakness in early adulthood
Myotonia and cataracts
unstable length mutation of a CTG repeat
affected if 50+ repeats
abnormal DMPK mRNA
indirect toxic effect upon slicing of other genes
describe cystic fibrosis
autosomal recessive
1 in 20 carriers
1 in 2500 newborns affected in UK
screening of newborns by immunoreactive trypsin level
confirmation by DNA testing and/or sweat testing
CFTR mutations
defective chloride ion channel
increased thickness of secretion
most common mutation: F508del
- prevents normal folding and insertion into the plasma membrane
what is cascade screening
identification of mutations permits prenatal diagnosis if desired and the subsequent testing of relative to identify carriers
What 2 things are needed for a relationship to be causal
- The exposure precedes the outcome
- The outcome is to some extent determined by the presence of absence of the exposure
What is the PPV
likelihood someone with a +ve test has disease
What is NPV
likliehood someone with -ve test doesnt have disease
