Physiology Flashcards
(231 cards)
1
Q
What are the 2 main structures of internal reproductive organs
A
Mullerian ducts
most important in female
inhibited in the male by AMH
Wolffian ducts
most important in the male stimulated by testosterone
lack of stimulation by testosterone means regression in female
2
Q
What is DHT role and what does it do
A
Testosterone inverted in the genital skin to the more potent androgen DHT (dihydrotestosterone) by 5-a-reductase.
DHT also binds to the testosterone receptor, but is more potent than testosterone.
DHT causes differentiation of the male external genitalia:
Clitoral area enlarges into penis
Labia fuse and become ruggated to form scrotum
Prostate forms
3
Q
Gonadal dysgenesis
A
Sexual differentiation is incomplete. Usually missing SRY in male, or partial or complete deletion of second X in female. Also used as a general description of abnormal development of the gonads.
4
Q
What is sex reversal
A
Phenotype does not match genotype, ie may be male genotypically but externally look like a female.
5
Q
What is intersex
A
Patients prefer to be known as someone with a ‘disorder of sexual differentiation’ or DSD.
Terms such as ‘pseudohermaphrodite’ and, ‘testicular feminisation’ are now obsolete
6
Q
What is androgen insensitivity syndrome
A
Testosterone is made but has no effect
7
Q
Describe complete AIS
A
Complete AIS - incidence 1:20,000
Appear completely female at birth and assigned female gender despite being XY.
Have undescended testes.
8
Q
Describe partial AIS
A
Partial AIS - incidence unknown as is probably a spectrum
Present with varying degrees of penile and scrotal development from ambiguous genitalia to large clitoris.
Surgery was universal but now fortunately considered optional or at least best delayed. Decisions made on potential. Very difficult for parents.
9
Q
What is 5-a-reductase deficiency
A
Incidence varies enormously as autosomal recessive and can depend on inter-related marriage.
Testes form, AMH acts, testosterone acts.
Internal structures form.
External structures do not develop.
May appear mainly female or may have ambiguous genitalia
The degree of the enzyme block varies and so therefore does the presentation.
10
Q
What is Turner syndrome
A
Turner syndrome: 1:3000
XO have failure of ovarian function.
‘Streak’ ovaries = ovarian dysgenesis - illustrates that we need 2 X’s for ovarian development.
Uterus and tubes are present but small, other defects in growth and development.
May be fertile…many have mosaicism.
Hormone support of bones and uterus
11
Q
What is CAH
A
Completeness of the block varies.
If enzyme absent then children may be wrongly gender assigned at birth…or may have ambiguous genitalia.
Also in CAH need to be aware of possibility of ‘salt-wasting’ due to lack of aldosterone, this can be lethal.
Need treatment with glucocorticoids to correct feedback
12
Q
What is the first different stage of becoming male and female in sexual differentiation
A
It is when the primitive sex cords express SRY to turn into either Sertoli cells in males or if they don’t express SRY they will become grandkids cells in females
13
Q
What is follicle initiation
A
Where a cohort of early follicles leave the resting pool and grow continuously
14
Q
What is called follicle recruitment
A
When follicles willl not continue to grow unless they reach the size at whic they respond to changes in FSH that occur in the menstrual cycle
15
Q
what are the hormones of HPG axis
A
Hypothalamus (RH)- Gonadotrophin Releasing Hormone (GnRH), (kisspeptin)
Pituitary (SH)- Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH)
Gonad- (F) Oestradiol (E2), Progesterone (P4), (M) Testosterone, (Inhibin and activin).
16
Q
what type of hormone is kisspeptin
A
peptide hormone
17
Q
what are the gonadotrophin hormones?
A
LH and FSH
18
Q
Describe the secretion of LH and FSH
A
Kisspeptin released from hypothalamus which coordinates the synthesis and secretion of GnRH. GnRH is released into primary plexus, into hypophyseal portal circulation, where it goes to anterior pituitary, binds to its receptor that is localised to gonadotroph cells to coordinate synthesis and secretion of LH and FSH.
19
Q
describe the 2 therapeutic exploitation of GnRH
A
Synthetic GnRH- same structure as endogenous GnRH
-same GnRH but produced from cell culture
-pulsatile administration, so is stimulatory. It allows people with puberty disorders to undergo puberty and can be used to stimulate fertility.
GnRH analogues-modified GnRH peptide structure
-based on primary sequence but changed
This means they have a longer half life, results in loss of pulsatility
-single bolus, long half life, loss of pulsatiility, inhibitory
can be agonists or antagonists
20
Q
what is puberty
A
Transition from non-reproductive to reproductive state
21
Q
what is adrenarche
A
change/increase in adrenal androgen secretin due to cellular remodelling of adrenal cortex through early years of development.
22
Q
what is pubarche
A
it is the result of adrenarche, result of increase in adrenal androgen secretion.
23
Q
what is precocious sexual development
A
Development of any secondary sexual characteristic
before the age of 8 in girls
before the age of 9-10 in boys
24
Q
what makes up a primordial follicle
A
In the foetal ovary, the surrounding cells condense around the oocyte and differentiate into the granulosa cells
The granulosa cells then secrete an acellular layer called the basal lamina
The whole structure is called the primordial follicle
25
what are oogonia?
Egg precursors
26
what factors determine growth of follicle in beginning?
The factors controlling initiation of growth and the early stages are largely unknown
FSH drives most of folliculogenesis but early growth is independent of FSH i.e. driven by local factors
Apparent in FSH-deficient patients or those with mutations of FSHr
Also means that even when FSH is suppressed eg. on COCP, the follicles will still continue early growth but then die
27
what happens to oocyte as follicle grows/antral development?
As the follicle grows, the oocyte is displaced to one side
28
how long are the stages of follicle growth
basal growth is 65 days plus follicular phase of menstrual cycle (15 days). approximately altogether 90 days
29
what are primordial germ cells?
cells that will become eggs or sperm
30
what is the difference between oogenesis meiosis and somatic meiosis
unequal division of cytoplasm during cytokinesis
31
What are the testes
Produce sperm and store it
Produce hormones which regulate spermatogenesis lie in scrotum outside body cavity, optimum temp for sperm production is 1.5-2.5degrees below body
Overheating of testes reduces sperm count
Well vascularised, well innervated
Normal volume of testes is 15-25ml measured by orchidometer
32
What is the follicular phase of menstrual cycle
It is between 5-10 days
| Where follicle recruitment occurs and the correct follicle is then chosen for ovulation
33
What cell is in close communication with the spermatogenesis?
Sertoli cells
34
describe the menstrual cycle
2 phases separated by ovulation
Cycle begins on day 1=first day of bleeding
Next 14 days are follicular phase i.e. growth of follicle
Ovulation occurs at end of follicular phase
Empty follicle becomes the corpus luteum
Next 14 days are luteal phase i.e dominated by corpus luteum
Menstruation occurs at the end
35
describe the hormones involved in menstrual cycle
Because it’s a cycle it doesn’t matter where we start……….at the end of the cycle, the corpus luteum which as we will come to see is the left-over follicle after ovulation, is dying and the progesterone that it was making falls. This high P was exerting negative feedback at level of hyp/pit, thereby keeping levels of LH/FSH low. As the levels fall, the brake on negative feedback is lost but in such a way that it causes FSH levels to increase preferentially. This stimulates follicles to grow and as they grow they make oestradiol. The E2 feeds back to hyp-pit and inhibits FSH release, so levels fall again. In the meanwhilst LH levels have been rising a little across the follicular phase and this allows a single follicle to grow and grow and become the dominant follicle. This DF which will makes massive amounts of E2. After 2 days of E2, which reach level of >300pmol, the negative feedback becomes positive and there is a huge release of LH which cause the egg to be released. The remaining follicle becomes the CL which makes prog. & this causes negative feedback again.
At the end of luteal phase, we have progesterone exerting neg feedback on hypothalamus and pituitary. Progesterone comes from CL.
If no preganancy, CL dies.
As CL dies, progesterone levels drop (decline). This removes that negative feedback. This allows the gonadotrophins to secrete again.
It allows for a selective release of fsh. This is known as the intercycle rise in FSH.
As FSH rises, it is going to pick up early antral follicles. Those early follicles, can respond to this increase in FSH and they start growing.
As they grow, oestrogen rises/ As oestrogen rises it will start exerting negative feedback again, causing FSH to drop.
As FSH drops, those follicles will start to die, because they are losing their stimulant to survive.
All except dominant follicle. As the dominant follicle survives, it grows at an exponential rate. It grows upto 20mm in size. It produces tonnes of oestrogen.
When oestrogen levels are sustained, over 300pmol, you then get the switch to positive feedback. This positive feedback triggers ovulation and a massive release of LH. This LH will trigger ovulation and formation and luteinisation of follicle which becomes corpus leuteum.
LH-lutenising hormone.
Cl prodces progesterone, which exerts negative feedback.
36
Describe follicular selection
Raised FSH present a “window” of opportunity
FSH threshold hypothesis
One follicle from the group of antral follicles in ovary is just at the right stage at the right time….
This becomes the dominant follicle which goes onto ovulate
Known as “selection”
Can be in either ovary
Oestradiol levels rise reinstating negative feedback at pituitary causing FSH levels to fall prevents further follicle growth
37
how does the dominant follicle survive the fall in FSH
Dominant follicle can be in either ovary. It may have increase number of receptors, to doesn’t need as much FSH to respond.
38
what is a special property of ejaculated sperm?
Ejaculated semen is coagulated
Prostatic and seminal vesicle secretions comprise seminal fluid which coagulates - prevents loss, later liquefies.
Movement through cervical mucus removes seminal fluid, abnormally morphological sperm and cellular debris.
39
How does a spermpass into cervix
Sperm passes into cervix
Cervical mucus is less viscous in the absence of progesterone allowing sperm to pass.
Sperm can inhabit cervical crypts which may form a reservoir. Some evidence of thermotaxis, but mechanism not yet elucidated.
Fertilisation typically within 24-48 hours but sperm have been recovered alive after 5 days.
40
what is the journey of the sperm to the egg?
Passage through uterus not well understood, currents set up by uterine or tubal cilia may have a role.
Chemoattractants released from the oocyte cumulus complex may attract the sperm.
Sperm become hyperactivactivated. Forceful tail beats with increased frequency and amplitude mediated by Ca2+ influx via CatSper channels.
41
what is acrosome reaction
Acrosome reaction occurs in contact with the zona –cumulus complex; the acrosomal membrane on the sperm head fuses releasing enzymes that cut through the complex.
Acrosin bound to the inner acrosomal membrane digests the zona pellucida so the sperm can enter.
42
what is capacitation
Capacitation is partly achieved by removing the sperm from the seminal fluid, also uterine or tubal fluid may contain factors which promote capacitation.
Biochemical rearrangement of the surface glycoprotein and changes in membrane composition must occur before the acrosome reaction can occur.
43
describe ovulation
LH spike causes resumption of meiosis and ovulation. Converts the primary oocyte to secondary oocyte plus 1st polar body.
Basement membrane breaks so blood pours into the middle.
Oocyte cumulus complex extruded out and caught by fimbrae of uterine tube.
Theca and granulosa become mixed and the empty follicle is known as the corpus luteum. It produces progesterone in the luteal phase.
44
how is cl maintained in pregnancy
CL rescued in pregnancy by hCG from embryo binding to its LH receptors. CL continues to produce progesterone and maintain endometrium.
45
name of CL after it shrinks
corpus albicans
46
describe sperm penetration to the egg
1. The acrosome reaction occurs in contact with the zona-cumulus complex. Sperm penetrate cumulus and bind to ZP2. Sperm enzymes cut through ZP and sperm fuses with plasma membrane3. Sperm taken in by phagocytosis. Phospholipase Zeta activated by basal Ca2+ inside egg and causes further release of intracellular Ca2+ leading to large Ca2+ spike.4. Cortical reaction as wave of Ca2+ sweeps around egg…release of proteases, peroxides and hyaline prevents polyspermy.
47
describe effect of testosterone andFSH on sertoli cells
Leydig cells contain LH receptors and primarily convert cholesterol into androgens. Intra-testicular testosterone levels are 100x those in plasma.
Androgens cross over to and stimulate Sertoli cell function and thereby control spermatogenesis.
Sertoli cells contain FSH receptors and converts androgens to oestrogen.
FSH establishes a quantitatively normal Sertoli cell population, whereas androgen initiates and maintains sperm production.
Leydig cells contain LH receptors and primarily convert cholesterol into androgens. Intra-testicular testosterone levels are 100x those in plasma.
Androgens cross over to and stimulate Sertoli cell function and thereby control spermatogenesis.
Sertoli cells contain FSH receptors and converts androgens to oestrogen.
FSH establishes a quantitatively normal Sertoli cell population, whereas androgen initiates and maintains sperm production.
48
what is a normal ejaculation volume
1.5ml-6ml
49
describe passage of sperm
Bulbo-Urethral Gland
Produces a clear viscous secretion high in salt, known as pre-ejaculate. This fluid helps to lubricate the urethra for spermatozoa to pass through, neutralizing traces of acidic urine.
Seminal Vesicles
Secretions comprise 50-70% of the ejaculate. Contains proteins, enzymes, fructose, mucus, vitamin C and prostaglandins. High fructose concentrations provide energy source. High pH protects against acidic environment in vagina.
Prostate
Secretes milky or white fluid roughly 30% of the seminal fluid. Protein content is less than 1% and includes proteolytic enzymes, prostatic acid phosphatase and prostate-specific antigen which are involved in liquefaction. High zinc concentration 500–1,000 times that in the blood is antibacterial.
50
describe what you would expect to find in semen analysis
```
Volume 1.5 – 6.0 ml
Sperm concentration >15million/ml
Liquefaction <30 minutes
Motility >40%
Progressive motility >32%
Vitality (live) >58%
Morphology (normal forms) >4%
pH >7.2
Leucocytes <1 million/ml
```
51
At what age does growth of follicles accelerate
Past age of 35-38 until u have depleted all your follicles
52
What are the two phases of the menstrual cycle
From first day of bleeding (first day of cycle) to ovulation is the follicular phase where there is growth of follicle and dominant follicle releases oestrogen.
Ovulation occurs at end of follicular phase
Then the empty follicle collapses and transforms into corpus leuteum. This is luteal phase where corpus leuteum releases progesterone
Menstruation occurs at end of the luteal phase
53
What two processes slow down the movement of sperm
Liquidefication of sperm
| Cervical crypts
54
What is capacitation
Capacitation is partly achieved by removing the sperm from the seminal fluid, also uterine or tubal fluid may contain factors which promote capacitation.
It is the biochemical rearrangement of the surface glycoproteins and changes in membrane composition that must occur before the acrosome reaction can occur
55
in what cells is aromatase enzyme found?
Granulosa only
56
what factors does menstrual cycle depend on and why are they all involved in starting menstruation?
it is an important and calorific process that requires input from lots of other systems in the body detecting fitness to reproduce.
With puberty, you have to be at a certain weight to start menstuation cycle.
-other complications involved in menstrual cycle. We can see the menstrual cycle is very much effected by the environment of the body and this is because we have to be fit to reproduce and the environment must be right.
The body needs to know the woman can cope with the burden of carrying a baby.
57
what processes occur before ovulation
ovulation occurs via cascade of events:
blood flow to the follicle increases dramatically
increase in vascular permeability increases intra-follicular pressure
appearance of apex or stigma on ovary wall
Local release of proteases
Enzymatic breakdown of protein of the ovary wall
12-18 hrs after peak of LH, hole appears in follicle wall and ovulation occurs
58
Describe the endometrial proliferative phase
Proliferative phase is stimulated by estradiol from the dominant follicle
Stromal cell division, ciliated surface. Glands expand and become tortuous, increased vascularity, neangiogenesis maximal cell division by days 12-14
When endometrium > 4mm induction of progesterone receptors and small muscular contractions of the myometrium.
59
describe the demise of the CL
If fertilisation does not occur, CL has an inbuilt finite lifespan of 14 days.
Regression of CL essential to initiate new cycle.
Fall in CL-derived steroids causes inter-cycle rise in FSH.
Cell death occurs, vasculature breakdown, CL shrinks. Over time it becomes a corpus albicans.
CL rescued in pregnancy by hCG from embryo binding to its LH receptors. CL continues to produce progesterone and maintain endometrium.
60
what subunit of hcg do pregnancy sticks identify
B subunit
61
describe the process of syngamy
Syngamy is the fusion of two cells or their nuclei in reproduction and this is what occurs between the sperm and egg nuclei.
1. After meiosis I the oocyte is haploid and contains 23 chromosomes, but each chromosome is bound to its identical sister chromatid.
2. At fertilisation the sperm binds to the ZP, penetrates it and fuses with the oocyte plasma membrane. This causes the increase in Ca2+ via PLC-zeta that then triggers the cortical reaction and also the completion of meiosis II and the expulsion of the second polar body. So the oocyte is now truly haploid.
3. The sperm nuclear membrane breaks down and the chromatin decondenses and the chromosomes separate (remember sperm is also haploid)
4. 4-7 hours after fusion of sperm and egg, the two sets of haploid chromosomes become surrounded by distinct membranes forming pronuclei. Each haploid pronuclei starts to synthesise/replicate its DNA in preparation for the first mitotic division
5. Then the two pronuclei fuse and the chromosomes become aligned on the mitotic metaphase spindle, the chromosomes move to their appropriate positions down the equator. So that each daughter cell will receive the chromosomes with their homologous pairs (i.e. so each has full 46, diploid number, 23 from dad, 23 from mum).
6. Mitosis is then complete and the one cell zygote has become a two cell embryo
When the sperm enters into the oocyte it causes the spike in Ca2+ due to PLC-zeta, this triggers the cortical reaction to prevent polyspermy and also the completion of meiosis II and expulsion of the 2nd polar body.
The haploid nucleus of the sperm transforms into the male pronucleus and the haploid female pronucleus forms. They replicate their DNA ready for mitosis.
Then the two pronuclei come together, the membranes break down and there is alignment of chromosomes down the spindle.
Each daughter cell will get 46 chromosomes. This is mitosis.
62
Describe the endometrial proliferative phase
Proliferative phase is stimulated by estradiol from the dominant follicle.
Stromal cell division, ciliated surface.
Glands expand and become tortuous, increased vascularity, neangiogenesis maximal cell division by days 12-14
When the endometrium >4mm induction of progesterone receptors and small muscular contractions of the myometrium
63
Describe the endometrial secretory phase
Secretory phase (luteal phase of ovary) 2-3 days after ovulation,
The gradual rise in progesterone causes a reduction in cell division.
Glands increase in tortuosity, and distend...secretion of glycoproteins and lipids commences
Oedema, increased vascular permeability arterioles contract and grow tightly wound .
Myometrial cells enlarge and movement is suppressed and blood supply increases.
64
Describe menstruation
Prostaglandin released causes construction of spiral arterioles. Hypoxia causes necrosis.
Vessels then dilate and bleeding ensues
Proteolytic enzymes released from the dying tissue
Outer layer of endometrium shed, 50% lost in 24 hours, up to 80ml is considered normal. Bleeding normally lasts +4 days
Basal layer remains and is then covered by extension of glandular epithelium
Oestrogen from follicle in next follicular phase starts cycle off again
65
Why do we have so many cocps
Because they all have different combinations of amount of oestrogen and type of progesterone within them
66
What is used for induction of labour at term
Oxytocin
67
What is used for induction of labour/termination in early term
Prostaglandins (not oxytocin-no oxytocin receptors)
68
What is post partum bleeding
Prostaglandins oxytocin, ergots
69
What is used to prevent premature birth
B2 adrenoreceptor agonists
Calcium channel blockers, Mg sulfate
Oxytocin inhibitors
70
What does osteoclasts do
Eats away bone
71
What does osteoblast do
Forms new bone
72
Describe structure of testis
Testis produce soerm and store it
Produce hormones which regulate spermatogenesis
Optimum temp for soerm production is 1.5-2.5 below body
Overheating reduces sperm count
Well vascularised and innervater
Normal volume of testis is 15/25ml measured by orchidometer, which is a series of spheres where each sphere represents one volume
They have lobes which contain seminiferous tubules. The tubules lead to an area called rete.
Rete then leads to epididymis and vas deferens
Soerm are constantly being made and stored in epididymis
On outside of seminiferous tubules, you have the Leydig cell
Spaces between tubules are filled with blood, lymphatic vessels, leydig cells and interstitial fluid
Leydig cells are male equivalent of Theda cells, they make testosterone
Sertoli cells have testosterone receptors, need testosterone to produce male genitalia
73
Describe pathway of ejaculation
Vas deferens smooth muscle contract
Sperm move along vas deferens and meet at seminal vesicles gland (contribute some things)
Sperm then move to prostate gland and high contributes secretions into soerm
Then vas deferens meet at the urethra
Causes ejacukation
Corpus cavernous fills with blood to create hydrostatic pressure responsible for erection
74
Describe process of spermatogenesis
Sertoli cells lie along the inside of seminiferous tubules, and have tight junctions between them called adluminal compartments
Sertoli cells communicate with sperm
Sperm move down as being made along side Sertoli cells, then are released into lumen of seminiferous tubules
Sperm start on outer edge of seminiferous tubules as spermatogonia (diploid)
Soermatogonia reproduce by mitosis
75
Describe ejaculation
Sperm made in seminiferous tubules, move to rete, then into vas deferens. Vas deferens contract by smooth muscle contractions stimulated from sympathetic nervous system. Sperm then move into the seminal vesicle gland which contributes proteins, enzymes, fructose (50-70% ejaculate), then move into prostate gland which secretes milky, white fluid and inserts enzymes, proteins, and the vas deferens then meet the urethra.
76
Role of bulbo urethral gland
secretes pre ejaculate, which is high in salt and neutralises the urethra, makes the urethra ready for sperm. It lubricates the urethra.
77
Process of spermatogenesis
New cycle every 16 days.
Diploid germ cells divide mitotically, called spermatogonia. Some spermatogonia can then become primary spermatocytes where they are then committed to meiosis, and the rest can continue to divide mitotically (hence male have lifetime supply of sperm). Primary spermatocytes complete meiosis 1 and turn into seconary spermatocytes which are now haploid. Secondary spermatocytes can then undergo further meiotic division to produce spermatids, which are now truly haploid, as M2 is complete. Spermatids lose their cytoplasm, and undergo spermiogenesis which is where they develop a tail and acrosome. Each division of becoming sperm is incomplete, as the cells are connected by cytoplasmic bridges, forming a syncytium, allowing synchronous development. At the end the bridges are broken.
Spermatogenesis happens next to sertoli cells. Tight junctions between sertoli cells provide an enclosed and protective compartment called adluminal compartment to protect from blood supply, luminal system and toxic chemicals.
78
What are catsper channels
Voltage gated calcium channels on sperm surface
Respond to pH and other factors of egg
As sperm get closer to egg, environment becomes more alkaline, opens catsper channels
Calcium rushes in, sperm becomes hyper activated? Soerm get closer to egg and start to swim faster
Tails beat more forcefully with increased frequency and amplitude
79
WhT is acrosome reaction
Acrosome reaction happens when soerm hits coronal radiate cells
Sperm then becomes hyper activated by the catsper channels and they start fighting their way through the cells
Acrosome reaction happens, sperm enzymes then cut through zona pellucida
Adhesion molecules enable the zona pellucida and the sperm to bind together momentarily
There are several of these factors, a major one called ZP3
These adhesion molecules between sperm and pellucida are specifies specific
As sperm cut through zona pellucida, the soerm and egg lipid membrane then touch? Causing fusion
Acrosome reaction occurs in contact with zona cumulus complex-when acrosome last membrane on soerm head fused releasing enzymes that cut through the complex
Acrosin bound to the inner acrosome life membrane digests the zona pellucida so the sperm can enter the oocyte
Acrosin is a digestive enzyme bound on inner acrosin all membrane
80
What causes the LH surge
Sustained high oestrogen
Then LH surge causes meiosis 1 to complete and ovulation
First polar body extruded and you are left with the secondary oocyte (primary oocyte converted to secondary oocyte).
81
What is oocyte cumulus complex
It is oocyte about to ovulate with cumulus cells in antral follicle
Basement membrane breaks so blood pours into the middle
Oocyte cumulus complex extruded out and caught by fimbrae of uterine tube which picks up an egg.
82
Effect of progesterone to uterine tube and endometrium
Makes endometrium secretory and receptive to implantation
Suppressed cilia in uterine tubes once oocyte has already passed
Makes cervical mucus viscous again to prevent further sperm penetration
Cells differentiate
When progesterone falls, it causes differentiation of the endometrium making it receptive
When it eventually disappears, endometrium falls apart, becoming receptive
83
What does the menstrual cycle achieve
Selection of a single follicle and oocyte each month
Regular spontaneous ovulation
Ensures correct haploid number of chromosomes in the oocyte
Cyclical changes in the cervix and uterine tubes to enable egg transport and sperm access
Preparation of the endometrium of the uterus to receive the fertilised egg
Support of the implanting embryo and endometrium by corpus lutetium progesterone production
Initiating a new cycle in fertilisation
84
How does the sperm prevent other sperm from entering the egg after it has entered it?
2 things
Enzyme similar to phospholipiase C present in sperm membrane, becomes activated when soerm enters egg
It causes the egg to release its intra cellular calcium -produces IP3
Then wave of calcium sweeps through egg
WAve causes a corticol reaction
-release of corticol granules that release professes that remove/hydrolyse all receptors in zona pellucida so no more sperm can bind (block polyspermy).
Also they release peroxides and enzymes that cross link and harden zona pellucida so they become impenetrable to even sperm enzyme
85
What is syngamy
Sperm enters egg, causes calcium increase in egg and completion of M2.
this expels a second polar body so left with truly haploid egg and truly haploid sperm.
Sperm nuclear membrane then breaks down and the chromosomes all separate out.
After 4-7 hours after fusion, both the male chromosomes and female chromosomes become surrounded by distinct membranes, forming pro-nuclei, now there are 2 pro nuclei.
The 2 pro nuclei are 2 sets of haploid chromosomes. These haploid structures then begin to synthesise DNA in preparation for first mitotic division. The pronuclei fuse together, and the mitotic metaphase spindle forms with the chromosomes assuming their position at its equator. Pairs of chromosomes-male and female, line up and position themselves on mitotic spindle.
Mitosis then occurs, first division of cell.
86
Descrive IVF treatment
Sperm and eggs are mixed and left overnight in a nutrient medium. The next day, if you see the 2 pro-nuclei in the egg, this is the first sign of fertilisation. Some people argue this is actually the start of life.
After 3 days, developing embryo has 6-8 cells, called a morula. After 5 days of fertilisation ( 2 pro nuclei shown), there are approx 100 cells and embryo has started to differentiate.
Embryo now called a blastocyst has an inner cell mass, a fluid filled cavity called blastocoele, and the periphery is surrounded by trophoblast, that will become the placenta. Intercell mass will become everything else. They are totipotent stem cells.
When the egg turns into a blastocyst, then it will implant into endometrium.
87
what cells are found in uterine tubes?
ciliated cells and secretory cells
88
effect of oestrogen on cells of uterine tube
When oestrogen high, it causes differentiation in cells of uterine tube. Cells differentiate and grow taller, ciliated cells start to beat, secretory cells secrete growth factors By the time of ovulation, there is a nice environment, inside uterine tube, for fertilisation,
89
what is window of receptivity of the uterine tube
Uterine tube shuts off at the end of menstrual cycle.
90
Endometriosis
Cells from endometrium move to uterine tube and block it.
cells of endometrium implant somewhere in pelvis where they respond to oestrogen and progesterone, hence they proliferate and differentiate then shed. This can be an inflammatory response. They can block fallopian tube or block outside of it as they move to pelvis.
91
adhesions in uterine tube
Pelvic inflammatory disease, inflammation in uterine tube.
92
What can block uterine tube
endometriosis, adhesions, infections, STIs, SURGICAL PROCEDURES.
93
What is ectopic pregnancy
embryo doesn't leave uterine tube.
94
What surgical procedures can be done to check if uterine tubes are blocked?
Laparoscopy & dye
-make incision in abdomen, put laparoscope through
inject blue dye through uterus, if blue dye emerges at fimbriae, then the tube is not blocked.
Done incase we suspect endometriosis
Hystero Salpingo Contract Sonography (HyCoSy)
-do not need laparoscope
-less invasive
-put cannula through cervix and inject ultrasound opaque dye
if black under ultrasound, dye is being reflected.
put ultrasound probe on abdomen and monitor progress of dye.
95
How do osteoblasts differentiate into osteocytes
By ...
96
What are the risks of treatment of contraception and the risks of no treatments
```
Risks of Treatment
Cardiovascular
Neoplastic
Emotional
Infection related
Allergic
Iatrogenic
```
```
Risks of no treatment
Childbirth related
Abortion related
Social costs
Economic costs
```
97
What are the benefits of treatment and benefits of no treatment
```
Benefits of Treatment
Non Contraceptive
Psychosexual
Choice
Sexual Health
Cost savings
Female equality
```
Benefits of no Treatment
Non interference
Population growth
Control of women
98
Different types of progestogens ad the latest one
Progestogens
Older (2nd generation) – Norethisterone (Norethindrone) & Levonorgestrel
Newer(3rd generation) – Desogestrel, Gestodene & Norgestimate (Noregestromin)
Latest (derived from Spironolactone) - Drospirenone
99
Why COCP such a good contraceptive
```
Oestrogens act
On anterior pituitary & hypothalamus
Directly on the ovary
On the EndometriumProgestogens act
On anterior pituitary & hypothalamus
Directly on the ovary
On the Endometrium
On the fallopian tubes
On cervical mucus
```
100
Benefits of cocp
```
1. Contraceptive
Reliable
Safe
Unrelated to coitus
Woman in control
Rapidly reversible
2. Non contraceptive
Halve ca ovary
Halve ca endometrium
Helps endometriosis, menorrhagia, dysmenorrhoea,
```
101
Risks cocp
Cardiovascular - Arterial – Progestogen , HBP, smoking
- Venous – Oestrogen-VTE-clotting disorders
(DVT, PE, Migraine)
Neoplastic - Breast, Cervix, Liver
Gastrointestinal– COH/insulin metabolism, Weight gain,
Crohns disease
Hepatic – hormone metabolisms, congenital nonhaemolytic
jaundices, gall stones
Dermatological – Chloasma, acne, erythema multiforme
Psychological – Mood swings, depression, Libido
102
Rules cocp
Start 1st packet 1st day of a menstrual period
Take 21 pills and stop for 7 day break (PFI)
Restart each new packet on 8th day (same)
Do not start new packets late
If late or missed pills in 1st 7 days, condoms
If missed pills in last 7 days no PFI
103
Combined vaginal contraceptive
Same as COCP except vaginal delivery (ring) for 21 days
Remove for 7 days
Adv – don’t have to take every day
Disadv - don’t have to take every day!!
104
Progesterone only methods
```
User Dependent Methods
POPs
- Desogestrel (Cerelle)
- Norethisterone
- Ethynodiol diacetate
- Levonorgestrel
- Norgestrel
Injectables
- Depo Provera (MPA) (12weekly)
- Noristerat (NET)Default Methods
Implants: Nexplanon
Norplant (LNG)
Hormone releasing IUCD:
Mirena IUS (LNG)
```
105
Why is cerelle better than older POPs
```
As effective as COCP
No oestrogen – CIs e.g. breastfeeding
Favourable side effect profile vs older POPS
Bleeding as predictable as COCP
12 hour window
```
106
IUCDs
Copper bearing intrauterine contraceptive devices are inserted into the uterus by suitably trained practitioners and may be left in situ long term and act by
1. Destroying spermatozoa
2. Preventing implantation – Inflammatory reaction and prostaglandin secretion as well as a mechanical effect
107
Types of IUCDs
1. Copper bearing Ortho T 380 – 8 -12yr
Multiload 375 – 5yr
Multiload 250 – 5yr (Standard
& Short)
Nova T 380 – 5yr
Nova T 200 – 5yr
GyneFix (IUI) – 5yr
2. Hormone bearing – Mirena (IUS) – 5yr
108
Benefits of IUCDS
```
Non user dependent
Immediately and retrospectively effective
Immediately reversible
Can be used long term
Extremely reliable
Unrelated to coitus
Free from serious medical dangers
```
109
Disadvantages of IUCDs
& risks of IUCDs
Has to be fitted by trained medical personnel
Fitting may cause pain or discomfort
Periods may become heavier & painful
It does not offer protection against infection
Threads may be felt by the male
Miscarriage if left in situ if a pregnancy
?ectopics
May be expelled
The uterus may be perforated
110
Contraindications and absolute contraindications of IUCDs
```
Absolute: Current pelvic inflammatory disease
Suspected or known pregnancy
Unexplained vaginal bleeding
Abnormalities of the uterine cavity
Relative:Nulliparity
Past history of pelvic inflammatory disease
Not in mutually monogamous relationship
Menorrhagia / Dysmenorrhoea
Small uterine fibroids
```
111
Condoms advantages for male and female
```
Male
Man in control
Protects against STIs
No serious health risks
Easily available (free at Family Planning clinics)Female
Woman in control
Protects against STIs
Can be put in in advance and left inside after erection lost
Not dependent on male erection to work
```
112
Condoms disadvantages
```
Male
Last minute use
Needs to be taught
May cause allergies
May cause psycho sexual difficulties
Higher failure rate among some couples
Oily preparations rot rubberFemale
Obtrusive
Expensive
Messy
Rustles during sex
Uncertain failure rate
```
113
Contraception caps
```
Diaphragm Caps
Made of latex
Fit across vagina
Sizes 55 – 95mm in 5cm jumps
Must be used with spermicide and left in at least 6 hours after sexual intercourseSuction (cervical) Caps
Made of plastic
Suction to cervix or vaginal vault
Different sizes
Must be used with spermicide and left in 6 hours or more
```
114
Caps advantages
```
Diaphragm Caps
Woman in Control
Can be put in in advance
Offers protection against cervical dysplasias
Perceived as “natural"
Suction Caps
Suitable for women with poor pelvic muscles
No problems with rubber allergies
Very unobtrusive
Woman in control
```
115
Caps disadvantages
```
Diaphragm Caps
Needs to be taught
Messy
Higher failure rate than most other methods
Higher UTI
Higher CandiasisSuction Caps
Needs an accessible and suitable cervix
Higher failure rate than diaphragm
Not easy to find experienced teacher
```
116
Fertility awareness
Prediction of ovulation ? 14/7 before period
Sperm can survive 5 days in female tract
Ova can survive 24 hours
Ova are fertilised in the fallopian tube and take 4 days to reach the uterus and implant
Cervical mucus is receptive to sperm around the time of ovulation
Use Periodic Abstinence/alternative contraception to avoid pregnancy
Time intercourse to pre-ovulatory phase to conceive
117
Natural family planning
```
Temperature
Rhythm
Cervix position
Cervical mucus
Persona
Lactational amenorrhoea (LAM
```
118
Fertility awareness advantages and disadvantages
```
Advantages
Non medical
Can be used in 3rd world
Allowed by Catholic church
Can result in closeness of understanding between partnersDisadvantages
Failure rate heavily user dependent
Requires skilled teaching
May require cooperation between partners
May involve limiting sexual activity
Can cause strain
```
119
Emergency contraception
Postcoital Pills
Up to 72 hours after unprotected sexual intercourse (UPSI)
Schering PC4 – prevents 3 out of 4 pregnancies which would have occurred
Levonelle – prevents
7 out of 8 pregnancies
ellaOne (ulipristal)– similarCopper bearing IUCDs
Up to 5 days after presumed ovulation or 5 days after one single episode of UPSI at any time of the cycle
Failure extremely rareLevonelle 2 consists of 2 tablets each containing 750 micrograms of Levonorgestrel
1.5mg one dose
120
Post coital pill
PC4
Lower failure rate in 1st 24 hours.
Causes nausea & vomiting in many women
Contraindicated during focal Migraine attack
Levonelle 2
Lower failure rate in 1st 24 hours
Very little nausea
Only contraindicated in women taking very potent liver enzyme medication (anti TB)ellaOne – ulipristal acetate
New selective progestagen receptor modulator (SPeRM)
Up to 120 hours
RR 0.58 pregnancy vs Levonelle
Possible slightly higher side effect profile – GI symptoms mainly
121
How do post coital contraceptions work
PC4 & Levonelle 2
Act by postponing ovulation in 1st part of the cycle – So beware!
??Act by preventing implantation in 2nd part of the cycleCopper IUCDs
Copper kills sperm in 1st part of the cycle
Device prevents implantation in 2nd part of the cycle
122
what is trophoblast
cells of blastocyst that invade
endometrium and myometrium (D 5-6)
- secrete ßHCG (Human Chorionic
Gonadotrophin
123
what is a chorion and an amnion
Chorion - that which becomes the placenta
| Amnion - layer that becomes the amniotic sac
124
functions of the placenta
```
Steroidogenesis – oestrogens, Progesterone,
HPL, cortisol
Provision of maternal O2
, CHO, Fats, AA’s
Vitamins, Minerals
Antibodies
Removal of CO2
, urea, NH4
, Minerals
Barrier - e.g. bacteria, viruses, drugs, etc
```
125
why the placenta is good at its job?
Huge maternal uterine blood supply - low pressure
Huge reserve in function
Huge surface area in contact with maternal blood
Highly adapted + efficient transfer system
126
what is the function of the amniotic cavity
Homeostasis - temp, fluid, ions,
Vital for development of certain structures
e.g. limbs, lungs
Protection - physical and barrier e.g. ascending
infection
127
Disorders of the placenta
```
Miscarriage - 15% (40%!?) pregnancies!
• Pre-eclampsia – 3-4% pregnancies!
• Hydatidiform mole
• Placental Insufficiency
• Transfer of other substances - drugs, toxins,
infections
```
128
Disorders of the amnion
* Polyhydramnios
* Oligohydramnios
* Premature Rupture of Membranes
129
what is the reason for the hormonal changes in pregnancy
Placental steroids
• Maternal steroids
• Fetal steroids
• Placental peptide hormones
130
what hormones cause changes in pregnancy
```
Placental steroidogenesis (7 – 8 weeks)
• Progesterone
• Decidualisation (CL)
• Smooth muscle relaxation – uterine
quiescence
• Mineralocorticoid effect – cardiovascular
changes
• Breast development Oestrogens (E1, E2, E3)
• E3 > E2 > E1
• Rely on androgens from fetus and maternal
adrenals
• Development of uterine hypertrophy
• Metabolic changes (insulin resistance)
• Cardiovascular changes
• Breast development
Placental CRH and cortisol
• Both increase from T2 onwards
• Cortisol
• Metabolic changes (insulin resistance)
• Fetal lung maturity
• CRH – possibly involved in labour initiation
(“placental biological clock”) Human placental lactogen (HPL)
• Similar to GH
• Metabolic changes – insulin resistance
• Possibly some role in lactation
• Prolactin
• Increases throughout pregnancy
• Breast development for lactation
```
131
What can be used to induce labour at term?
Oxytocin
132
What can be used for induction of labour/termination in early term
Prostaglandins, not oxytocin as there are no oxytocin receptors
133
What can be used for post partum bleeding
Prostaglandins, oxytocin ergots
134
What can be used to prevent premature birth?
Beta 2 adrenoreceptor agonists
Calcium ion channel blockers, Mg sulfate
Oxytocin inhibitors
135
Describe myometrial activity, coupled to slow waves and calcium levels, how this creates contractions
Waves of electrical activity
-due to inward currents.
-positive currents that would eventually pass a threshold, depolarising membrane, that would activate VGCCs, calcium enters cells increasing intracellular calcium, leading to contraction. Once past threshold, ap generated, doesn’t last forever.
Various mechanisms then reduce membrane potential
Cycle kicks in again.
The reason that the events are coupled, is because of the gap junctions that enable the electrical coupling between the ICCs and the smooth muscle cells.
The cells are sensitive to hormones such as oestrogen, progesterone, oxytocin. These modulate the slow waves of ICCs and smooth muscle responses. Cellular mechanisms of smooth muscle contraction
• Positive currents cause depolarisation then activation of calcium channels.
• Calcium entry increases calcium level
• Calcium binds to calcium calmodulin
• causes activation of myosin light chain kinase.
• MLCK then phosphrylates MLC causes actin interactions
• Leading to contractions
This happens in all smooth muscles.
When it is modulated by neurotransmitters and hormones, they act via cellular signalling on receptors.
Eg oxytocin,
• Oxytocin binds to Gq coupled receptor
• This then activates phospholipase C and converts PIP2 into IP3 and DAG.
• IP3 binds to IP3 receptors in intracellular store. This causes calcium from intracellular store to be released into cytosol, causing increase in calcium.
This is Calcium induced calcium released contraction mechanism. This is happening in one cell only.
However the smooth muscle cells are all working together in syncytium, via the gap junctions. Hence if electrical activities are happening in one cell, depolarisation can be transmitted across to neighbouring cells through gap junctions. 2 main mechanisms to reduce calcium
• The cytosol level can be reduced by calcium pump which can reduce calcium levels by moving calcium out of the cell or by moving it back into the calcium stores within the cell.
• Or we can use sodium calcium exchanger to get rid of the calcium from the cytosol.
Some of the cells use mitochondria as a reservoir of calcium. Some of the calcium in the cytosol can be taken into mitochondria
136
Give examples of neurotransmitters, sex hormones and therapeutic drugs, how they can modulate that activity and when they can be used
Sympathetic innervation-mainly noradrenaline, ATP. Contain on alpha and beta adrenoceptors.
With sympathetic innervation, noradrenaline can act on alpha or beta adrenoreceptors on smooth muscle cells.
Activation of alpha1 receptor causes contraction (increase calcium concentration in smooth muscle cell).
Beta 2 receptor activation causes relaxation
This is the same in vascular smooth muscle and airways.
Activation of alpha 1, it is a Gq/11, coupled with PLC, PIP2 turns into IP3 and DAG, IP3 then increases calcium concentration.
B2 is a Gs receptor, activates Adenylate cyclase which turns ATP into cAMP, then activates Protein kinase A which causes relaxation.
Stimulation of B2 adrenoceptors on smooth muscle (vascular, airway, myometrial) produces relaxation
• Gs coupled, increasing Camp levels.
• Activates protein kinase A, causing relaxation.
• Reaxes uterine, airways and vascular smooth muscles
137
Describe osteoblasts differentiation
In notes
138
Describe induction of osteoclasts by tank ligand
Rank ligand, on notes are
139
Describe Wbu signalling pathway
On note
140
Benefit of T1w / T2W images and MRI/NMR images than normal medical x Ray images
On sheet of paper
141
```
Describe what scans can be used for
Gross structural and pathological change
Anatomical developmental change
Metabolite levels
Blood flow
Metabolism
Connectivity
Functionality
Receptors
```
Pic on phone
142
Recap skeletal muscle contraction
An action potential in a MN causes the axon to release ACh which depolarises the muscle cell membrane.
Transverse tubules depolarise the sarcoplasmic reticulum.
Calcium is released and binds to the troponin complex. Tropomyosin shifts and unblocks the cross bridge binding sites
The thin filaments are ratcheted across the thick filaments by the heads of the myosin molecules using energy from ATP.
143
Describe muscular contraction
Motor neurone stimulates muscle to contract, there is release of calcium in muscle cell.
Within the sliding filament model, ATP binds to the myosin head (which has a globular head and a tail). ATP is then hydrolysed and a phosphate bond breaks.
This generates energy to produce contraction, releasing ADP and inorganic phosphate. The myosin head then becomes cocked and ready to act. When calcium is present, it enters this high energy state where it binds to CnC, causing it to change its binding on CnI, which causes change of CnT, so myosin head can now bind to actin. It bins to actin, and pulls actin across and causes movement.
ATP then needed for cycle to occur again.
There is a protein called troponin, which forms a complex with tropomyosin. When calcium binds to troponin, it causes a conformational change to the troponin and this causes a shift in the tropomyosin (as the troponin is bound with tropomyosin). This shift in tropomyosin then uncovers the myosin binding sites on the actin. This then permits the myosin head to bind to the actin and then ratchet along the thin filaments.
144
What is ALS
Amyotrophic lateral sclerosis
MN degenerative disorder that ultimately causes death by respiratory failure
145
What is myasthenia gravis
Autoimmune disease that blocks and destroys AchRs at NMJs leading to muscle weakness.
Body producing antibodies to AchR destroying them, causing muscle weakness, esp when doing exercise
146
What are the result of changes in isoform to myosin and troponin
Myosin isoforms of myogibrillar proteins give alternate splicing or promoters
Myosin isoforms give diff chemomechanical transduction, ATP hydrolysis, shortening velocity
Troponin and tropomyosin isoforms determine sensitivity to calcium ions
Turin isoforms contribute to elastic properties
All result in resistance to fatigue
147
Functions of skin
-> It acts as a barrier, that stops microbes going inside as well as physical objects e.g. pencil!
-> acts as protection against: dehydration (epidermis. Keratin holds water, lipids stop it evaporating.), infection (Epidermis: tight, imprevious barrier) injury/abrasion (all layers. Epidermis is strong, rapid healing, thick where friction occurs. Dermis has collagen-tough, leathery. Hypodermis provides cushioning effect), solar radiation (epidermis-stratum corneum and melanin pigment. Horny layer also stops some ultraviiolet radiation, the thicker the skin, the more protection).
-> It is also a homeostatic organ, regulating body temperature via sweat production and blood flow, e.g. gym and snow. It is not a fluid homeostatic mechanism, as we do not adjust our fluid volume by controlling sweat production, but we do lose water through skin.
-> Skin is also a very important insulator, we all have fat (subcutaneous)
-> The skin is an extremely important for sensation
-> The skin is also a secretory organ, it makes vitamin D for us
->repair 2) Thermoregulation
Hypodermis (insulation); thermoreceptors; blood supply regulation, sweating.
3) Sensation
Nerve supply and various receptors
4) Repair
Epidermis – normal proliferation, and dermis – fibroblasts fill gaps with new collagen that epidermis can attach to.
5) Vitamin D3 production
Epidermis.
Fibroblasts in dermis can produce new collage if injury or gap in dermis.
Vit d production happening in basal epidermis.
148
what are the 3 layers of skin
Epidermis, dermis, hypodermis
149
what is a friction blister
What is a (friction blister)?
- > These are the watery type blisters. It is when the top layer of skin, rubs against the basal cells (bottom layer of epidermis). This causes the spiny cells to get crushed, so the watery fluid is the content of all the spiny cells that burst.
- > Then because there is a lot of protein in this fluid from the burst cells, there is a lot of osmotic pressure. So water gets pulled in via osmosis as a transudate.
150
What are the structures of the epidermis
1. Stratum basale: most inner proximal layer consisting of stem cells that divide and push upwards. Found on top of the dermis. Cells constantly divide and differentiate. As they differentiate they move upwards distally to outer layer.
2. Stratum spinosum. Cells still have nucleus, and cytoplasm. They are differentiating, not dividing anymore.Contain desomosomes are junctions which attatch the cells to each other, this means that this part of the skin is tightly coherent and stuck together. This is a very strong cellular adhesion, which is why the skin is a good barrier. The cells in the stratum spinosum get pushed up by the dividing cells beneath.
3. Stratum granulosum, 1-4 layers of cells containing prominent granules of 'keratohyalin'.they will develop into the protein keratin, main component of the skin.
So cells make lots of keratin. Some other of granules are called lamellar bodies, have a lot of lipids in them. These are differentiating to form outer most layer called stratum corneum.
4. Stratum corneum,The most functional layer of skin, or protective layer. Usually many cells thick on parts of skin such as feet and fingertips.
These are squamous cells, flat flake like cells.
In case of epidermis, they have lost their nuclei. There is almost nothing lost in there except keratin and lipid on outside.
They are cornified-full of keratin which is a touch resilient protein helps the layer of the skin to resist friction and impact. The lipids help to waterproof the skin, so non polar lipids, are the most water proof kind. They are in between the cells and come from the lamellar bodies that were in this stratum granulosum. This is the structure of the stratum corneum. Stratum corneum: these are keratin-packed dead (anucleated) cells that slop off eventually.
151
What structure allows epidermis to access nutrients from blood vessels?
Dermal papillae.
152
Describe the role of the thermo-receptor, meissner's corpuscle, nociceptor, pacinian corpuscle
Thermoreceptor senses heat or cold.
Meissner's corpuscle senses 'touch'.
Merkel cells in basal epidermis also sense light touch.
Nociceptor senses pain (free nerve endings)
Pacinian corpuscle senses 'pressure'.
Also found from hypodermis.
153
Describe the ventricular system
CSF made in the choroid plexus, CSF flows from the ventricles down to the brainstem and spinal cord. So CSF is made from choroid plexus inside brain, within ventricular system, it then travels down from spinal cord to these ventricular apertures near the cerebellum where it can then surround the brain. Once it surrounds brain it gets recycles and absorbed by the blood vessels in the subarachnoid space. Entry at choroid pleuxus, exit at subarachnoid space
• It is constantly circulating, proving a salty saline environment for brain to live in, and allows nutrients and waste removal for the brain.
154
What is the purpose of CSF
CSF protects the brain from physical and chemical injury. It regulates intracranial pressure, and is essential in exchanging nutrients and waste products between blood and the CNS.
155
Describe the cerebral vasculature
Two pairs of arteries supply blood to the brain, the vertebral arteries and the carotid arteries. Branches from the arteries supply blood throughout the brain. They also form an interconnected structure called the circle of Willis. Most of the lateral surface of the cerebrum is supplied by the middle cerebral artery. Most of the medial wall of the cerebral hemisphere is supplied by the anterior cerebral artery.
156
What are the 12 nerves and their roles?
Pic on phone
157
List the features of different glial cell types
Microglia
-Immunological cells, phagocytes
-Regulate programmed cell death
-Perform health checks by interacting with dendritic spines
-Neurogenesis (cell birth)
-Modulation of synaptic transmission.
Oligodendrocytes (CNS) and Schwann cells (PNS)
-both myelinate axons
-myelin acts as insulator, to stop cross talk, and stop dissipation of current. It speeds up how fast an action potential is therefore able to travel.
-wrap around axons
-in picture, axons cut coronally. Dots are microtubules, actin filaments, microfilaments. The rolls around are the myelin, formed by oligodendrocytes or schwann cells.
Astrocytes
-Regulate contents of the extracellular space
-Express receptors
-Release neurotransmitter
158
What makes a neurotransmitter?
• First, it has to be synthesised and stored in the presynaptic neurone.
-it has to be synthesised there because synaptic transmission is fast. You will run out quickly if it is made somewhere above and then has to travel down below-supply will not be meeting demand.
• So we need there to be an active pool of neurotransmitter being created at all times, in order to be ready for the next stimulus to take place for it to be released.
• Neurotransmitters must be released upon stimulation.This is common for all types of neurotransmitters. In this instance it is the arrival of an action potential-the change in voltage that happens upon the arrival of an action potential in the synaptic bouton, that activates voltage gated calcium channels (in the membrane of synaptic bouton). Calcium then rushes into the cell and activates proteins that are present on the vesicles, signalling them to fuse with the pre synaptic membrane.
-A stimulation is required for the vesicular proteins to be activated and then fuse with pre synaptic membrane.
159
Describe how an action potential occurs
Action Potential Propagation
At rest, we have voltage gated Na+ K+ channels closed
Then depolarising stimulus, nicotinic ACth receptors have bound AcTH
Channels open, causes small depolarisation
This activates some voltage gated Na+ channels in membrane of that neurone
This causes further influx of Na+ ions, further influx of positive charge into cell-further depolarisation. It is like a domino effect. The more Na+ influx into the cell, the more Na+ channels open, until we have a big event where a large amount of sodium channels opens simultaneously.
So we have a great influx of sodium, and a great amount of depolarisation, huge increase in the charge of the cell.
Voltage gated sodium channels then deactivate (do not close, are just deactivated).
Na+ channels are plugged. NOT CLOSED.
Once they are plugged, we have no further influx of sodium ions into the cell.
The voltage gated potassium channels are opened, potassium will then flow out of cell down its concentration.
As we are losing positive charge, the voltage of cell decreases.
At the very end, there is an area of undershoot, where k+ channels open for too long, so potential decreases slightly.
Then na+ k+ pump (ATP driven) acts to restore this membrane potential to -70, 3Na+ out, 2K+ in. This maintains the resting membrane potential.
This sequence of opening and closing voltage gated channel, dictates that an action potential will travel in one direction, down an axon.
If we have an action potential where our sodium channels open and huge influx of sodium, then one side of the membrane will be hugely influenced by this depolarisation, so we will get opening of sodium channels in the adjacent part of the membrane. So the action potential is moving down the section of the axon. Before part of membrane, is now going into phase 4, plugged Na channels and opened K+ channels.
This means that when we have a depolarisation in one part of membrane, action potential can only travel in one direction. It cannot travel backwards, because the sodium channels in part before it are plugged. So this mechanism ensures that the action potential will sequentially move in one direction, down the axon.
So we have action potential generation, and action potential propagation.
What happens when action potential arrives in synaptic bouton?
• It arrives, voltage gated calcium channels open
• Voltage gated calcium channels open
• Have influx of calcium into the presynaptic bouton
• This initiates vesicle fusion with presynaptic membrane, and emptying of neur transmisster contained in the synaptic vesicles into synapse, to interact with receptors post synaptic ally.
• Finally, the molecule that is released, must cause some form of change in the post synaptic cell. This change is induced by the neurotransmitter binding to receptors and then activating them, ad causing some change in the physiology of the post synaptic cell.
• Middle section is a common mechanism for most neurotransmitters-when discussing glutamate and gaba and glycine. First and third are different however.
160
Describe different glutamate receptors
Ionotropic and metabatropic
Three classes of different ionotropic receptors: AMPA, NMDA, Kainate.• The reason they have these names is whilst they all have the endogenous naturally occurring glutamate agonist, they are all selectively activated by a non naturally occurring exogenous compound. • AMPA receptor is selectively activated by an AMPA molecule
• NMDA receptor by NMDA molecule
• Kainate receptor activated by Kainate or kainic aicd. • When ampa and kainate receptors open, when they are activated by their agonists, you get influx of sodium and efflux of potassium
• But NMDA also enables calcium influx when it opens. This is important in synaptic plasticity, but also in excitotoxicity. • The majority of AMPA, NMDA, and kainate receptors, can be found post-synaptically.
• However, there are instances where these receptors are found pre-synaptically and on glia cells as well. BUT PREDOMINANTLY FOUND ON POST SYNAPTIC NEURONES
161
Describe how LTP is created
| -long term potential
• We will get neurotransmitter released, and binding at first, to the AMPA receptors.
• This will enable Na+ to enter the cell, and this will depolarise that post synaptic cell.
• Now the cell is depolarised, this causes the magnesium block to leave the NMDA receptor channel.
• So now we can also get the activation of the NMDA receptors.
• The NMDA receptor activation, further depolarises the cell, because we have influx of both sodium and calcium.
• This calcium influx, influences the cell and causes the cell to make and traffic more AMPA receptors to the post synaptic membrane.
• This means that when we have further stimuli, -more AMPA receptors in the membrane, so increase more current into cell
-we get an even larger depolarisation than before.
• Calcium also activates enzyme called P-CamKII (cam kinase 2)
• Cam-Kinase phosphorylates these AMPA receptors, and this enables the AMPA receptors to pass more current and ions through, per channel opening. –IT INCREASES THE PERMEABILITY OF THOSE AMPA RECEPTORS.
• So we have calcium causing more ampa receptors to be trafficked to membrane, then become more efficient, they are able to pass more current because they have been phosphorylated by CAM-kinase II, which was activated also by that calcium.
-This causes LTP-Long term potentiation.
-more receptors in membrane, we have been able to increase ion flow per stimulus, so amount of response we are able to induce in our post synaptic cell-is now much increased (potentiated).
-this potentiation is deemed long term because we have made more proteins that we have inserted into post synaptic membrane, and we have phosphorylated them as well.
These changes aren’t readily reversible within a matter of seconds and they persist long term for hours and days.
162
Describe excito-toxicity
• Excitotoxicity occurs when we have too much excitation.
• Under some pathological conditions, there can be damage to the functioning of vesicular glutamate transporters (transporters that are pumping glutamate made in cytosol into vesicles ready for release). If these are not functioining properly, then you have a lot of glutamate, remaining in the cytosol.
• This is a problem, because these excitatory amino acid transporters work on the basis of taking high concentration of glutamate and put them into low concentrations. (synaptic transmission, dumping glutamate into cell as there is high concentration in synapse). If they are not working anymore, and suddenly there is a high concentration of glutamate in the cytosol, this causes the transporters on membrane to reverse in their function, and they start to pump glutamate out of cell.
• So glutamate released out of cell, without presence of stimulus.
• This means that glutamate is released by cell without presence of stimulus-no action potential has arrived.
• We then end up with activation of those ampa receptors, and activation of the ampa receptors, and activation of NMDA receptors again, and influx of calcium into post synaptic cell, in an uncontrolled fashion.
• When we have release of glutamate when an action potential occurs, that is controlled release. This is uncontrolled release.
• When we have uncontrolled levels of calcium in that post synaptic cell, it can cause damage to mitochondria, and stop cellular respiration from taking place. Cellular respiration is an important function for all cells to live, we all need ATP to function.- if mitochondria are damaged that is big deal.
• It can also cause oxidative stress by the formation of free radicals which can damage the intracellular environment even further, and can initiate the cell to undergo apoptosis.
-excessive calcium will lead to cell death through one or all three of these events taking place.
What causes excitotoxicity?
• Stroke can cause ischemic damage, resulting to excito-toxcitity as a result of any clots or leaks
• Excitotoxcity also linked to autism and Alzheimer’s disease –not known for sure, but evidence from laboratory that they might be.
163
What are diff glutamate receptors and where are they found
Ionotropic, FOUND ON post synaptic neurones
AMPA, NMDA, kainate
Metabotropic, Group 1 found post synaptically, group 2& 3 found pre synaptically. P• ost synaptically, group 1 receptors contribute to LTP and therefore plasticity.
-there would be mGlu1 and 5 receptors in that membrane which would then help with increasing intracellular calcium concentration by liberating the calcium from the ER.
-contrinuted to increase AMPA receptor manufacture and phosphorylation
• Post synaptic receptors of group 2 & group 3, their main function is to inhibit further neurotransmitter release. Once they are activated, they can stop further release of any neurotransmitter as well.
164
where are GABA (inhibitory) receptors commonly found?
post synaptically, but with just glutamate, they can be found pre synaptically
165
Describe the multiple binding sites on GABA a receptor
```
Multiple binding sites:
Agonists/antagonists e.g. GABA
Benzodiazepine binding site
Channel modulators e.g. GA, alcohol
Allosteric modulators e.g. Barbiturates
Channel blockers e.g. Picrotoxin
```
166
where is glycine made
nerve terminal
167
what is the most common glycine receptor form?
Subunits are a1-a4, and 1 beta subunit. Most common receptor is 3 alpha, 2 beta, or 4 alpha, 1 beta
168
Describe startle goats
There is no glycine protein present at post synaptic membrane of these animals/humans.
Or the glycine receptor protein is non functional. As a result, in thee animals, there is deficiency in being able to produce inhibition, because they do not have a functional subset of these receptors. When goats are scared there is a huge activation of excitatory and inhibitory mechanisms, animal is in fight/flight response. But its glycine receptors are not working therefore it has an imbalance in the inhibition excitation. Not enough inhibition and too much excitation. So what happens is a transient seizure is induced in the goats They go into a massive tonic phase of muscle contraction, as a result they go stiff and fall over. But it is okay-this only happens in juvenile animals as the body learns. They body sorts this out as the goats mature, because GABAa receptors are upregulated to compensate and stop this from happening. Gaba a is also a ligand gated chloride channel, so can restore back inhibition,
169
What happens if we do not terminate effect of neurotransmitters?
Things like excitotoxicity take place, in the case of glutamate.
170
What are the inhibitory neurotransmitter mechanisms?
Cl- influx
K+ efflux
Two types of gaba receptors, GABA A which are ionotropic, and GABA b which are metabotropic
Glycine receptors are ionotropic, glucine is a co ligand for NMDA receptor
171
Example of drug that increases NA in brain
Amphetamine, psycho stimulant, induces excitement and produces pleasurable effects. Acts as an indirect sympathomimetic, enters vesicles, displaces NA into cytoplasm, increasing NA leakage out of neurone, increasing levels in synaptic cleft, causing excitable/pleasurable behavioural response in taking amphetamine.
172
What is the precursor molecule of dopamine?
Tyrosine
173
Name of serotonin auto receptors
5HT1D autoreceptors
174
What are the 2 diff amino acids between oxytocin and vasopressin
At position 3, vasopressin has phe whereas oxytocin has lle
At position 8, vasopressin has arg, oxytocin has leu
175
Describe the effect of oxytocin in voles
Voles are monogamous
When find someone, stay with him for their whole life
Voles have high levels of oxytocin receptors in reward centres of brain
Tells you oxytocin is important for socialising,Making pairs. It is known as the love hormone
Mice are promiscuous animals, have low levels of oxytocin
176
What acts as the most powerful lens
Cornea
177
What is the role of the lens of the eye
Provides additional fine focus so you can focus accurately but also allows you to focus on different distances
178
What was the experiment that women did to show linkage of their menstrual cycle ?
Pic on phone
179
Describe how photoreceptors work?
Photoreceptors detect light.
RODS- super sensitive photoreceptors, used for night vision, when light levels are too bright, they simply saturate and become non functional.
Cones- less sensitive, able to work well in high light levels.
Opsins- found in photoreceptor, one of the membrane bound proteins. They are the protein compoentn of photopigment, and the other component is 11 cis retinaldehyde (retinal)
Retinal + opsin = photopigment
Retinal is made of carbon chain, each carbon bond is a trans bond, except fot the 11th bond whoch is a cis bond, called 11-cis retinal
When light strikes the cis bond, the bond ruptures and reforms in the trans configurationn, forming all trans retinal.
The trans config is more stable and acts as an agonist, it is attached to GPCR. When all the trans bondsbinds, it activates the G protein, which activates the enzyme, causing aa fall in cGMP, a cGMP falls, some diffuses away from Na+ channels, so they close. Overall have closure of Na+ channel because of photon of light.
180
Describe the action of the cochlear amplifier ?
As basilar membrane moves up, it pushes against the tectorial membrane.
Movement of the tectorial membraine makes the hair bundle lean.
As it leans, it opens up the channels on the hair cell. This allows influx of positive ions, increasing voltage inside the cell, causing cell to contract and go smaller.
As cell contracts, it pulls the basilar membrane toward the tectorial membrane, as it does this, it causes more pressure on the tectorial membrane, because the two membranes are now closer together, which causes an influx of positive ions into the inner hair cell.
So movement of basilar membrane towards the tectorial membrane, causes inner hair cells to be leant on by tectorial membrane, causing opening of channels on inner haircell and influx of positive ions into the inner hair cell. So by contracting, it pushes up the basilar membrane, which then allows the inner hair cell bundle to lean even further, , allowing influx of positively charged ions, causing increased firing of auditory nerve.
In this way we are getting amplification of whatever signal is coming in.
Without this amplification, it would be difficult to hear particularly quiet sounds. It is more active during quiet sounds than loud sounds, and it also affects the tuning of the auditory nerve fibres.
181
How do you know beta activity is associated with Parkinson’s disease
Beta level is very high and movement is inhibited in pd patients
When you do something to reduce it, like give them dopamine, or do deep brain stimulation, you get reduction in beta activity and their movement improves.
182
What is forward model
When u move, a copy of that movement is sent to another part of your brain
183
What does freezing mean?
Walking in little steps
184
Describe importance of beta frequency
High prevents movement
Low allows change in sensory state
Movement control is a predicted thing
It has other things involved also like cerebellum which looks for mistakes in movements but also checks that what actually happened was what was expected to happen.
If problem wit comparison, cerebellum will try and make that right by learning or by stopping
Allows us to understand Parkinson’s and tarrets (tic) syndrome
185
WhT is hyperalgaesia and allodynia
Hyperalgaesia is increased sensitivity to pain
Allodynia is painful sensation from innocuous stimulation
186
What are the cutaneous skin receptors of the somatosensory system
Superficial
-Meissners Corpuscle, rapidly adapting, respond precisely to onset
-Merkel's disks, slowly adapting, best at reconstructing actual stimuli
Both are tactile afferents, very sensitive to small depolarisations, which then excite them.
Deep-mechanosensitive afferents
-Pacnian corpuscle, detect vibration, best at high frequency.
-Ruffinis corpuscle, least understood stretch, detect slippage or non slippage
187
What are the receptors of the somatosensory system
```
Proprioception=muscle spindles
Tactile afferents (discriminative touch)=
Cutaneous
-Meissners corpuscle (RA)
-Merkels discs (SA)
Deep
-Ruffini Corpuscles (sa)
-Pacinian corpuscles (ra)
```
188
What is the hormone that tells you to stop eating
Leptin, discovered by Jeffrey Friedman
189
Describe location of declarative and non declarative input
Declarative is for facts and events in hippocampus
| Non declarative is procedural memory in striatum
190
What are the 2 parts of the hypothalamus that control food intake?
VMH- lesion will cause obesity, over eating
| Lh, lesion will cause mouse becoming thinner, anorexia
191
alpha MSH and CART
ALPHA MELANOCYTE STIMULATING HORMONE: found in arcuate nucleus.
CART- cocaine and amphetamine regulated transcript, arcuate nucleus.
192
Where is the hippocampus located
Medial temporal lobe underneath temporal bone
193
Describe the process of memory
There is activation of the cell assembly by an external stimulus.
Reverberating activity continues activation after the stimulus is removed.
Hebbian modification strengthens the reciprocal connections between neurones that are active at the same time.
The strengthened connections of the cell assembly contain the engram for the stimulus.
After learning, partial activation of the assembly leads to activation of the entire representation of the stimulus.
so you remember that the stimulus is a circle.
194
What are the 2 types of amnesia
Retrograde amnesia (loss of memories they already have)
Anterograde amnesia ( inability to form memories after trauma)
195
What are the 2 things allowing us to classify sound?
Place of articulation
| Manner of articulation
196
where is acetylcholine or hypocretin (orexin) inn brain found
Acth-basal forebrain
| Orexin -lateral hypothalamus
197
what gland produces melatonin
pineal
198
what 2 hormones important in causing sleep
adenosine and orexin (hypocretin)
199
wHAT are EEG
Signal waves from brain, showing brain waves-
200
Fluent progressive aphasia
Normal sounding speech rate and production empty of content
Begins with subtle word-finding changes
Generic word and pronoun use spontaneous speech
Profound single word comprehension difficulties
Location of pathology
Anterior temporal regions
Typical pathology
TDP-43 proteinopathy [FTD-TDP]
201
Wernickes aphasia
AKA ‘Receptive aphasia’ or ‘sensory aphasia’
Speech: Fluent, often with meaningless phonological strings
Follows damage to: posterior regions of language network
Typical pathologies: penetrating brain injury; cerebral haemorrhage
202
Nonfluent progressive aphasia
Slow, distorted, agrammatic speech production
Begins with subtle changes – progressive course
Phonological and grammatical errors in spontaneous speech
Single word comprehension well preserved
Difficulty understanding sentences
Typical pathology
Primary tauopathy [FTD-Tau]
203
Logopenic progressive aphasia
```
Begins with subtle word-finding changes
Poverty of speech output
Occasional errors in syntax and phonology; poor sentence repetition
Posterior perisylvian pathology
Typical pathology
Alzheimer’s disease
```
204
What are the 2 theories of emotion?
James- Lange
We experience emotions in response to physiological changes in our body
Cannon-Bard
We can experience emotions independently of emotional expression (dissociations)
Emotions are produced when signals reach the thalamus either directly from sensory receptors or by descending cortical input
205
What structure is important for emotional experience?
Cingulate cortex
206
What are features of limbic system
```
Cingulate gyrus
Parahippocampal structures
Septal nuclei
Amygdala
Enthorinal cortex
Hippocampal complex
-dentate gyrus
-CA1-CA4 subfields
-subiculum
```
207
Describe cingulate gyrus
Role in complex motor control
Pain perception
Social interactions -mood
208
What region of brain is important in fear
Amygdala
209
What does temporal lobe contain
Temporal cortex, amygdala, hippocampus
210
Difference between neurology and psychiatry
Neurology is the branch of medicine focused on nervous system disorders
Psychiatry is the branch involved in disorders that affect the mind or psyche
211
What are the purpose of anti depressants
Antidepressant drugs
Increase in monoamines may ‘normalise’ presynaptic and postsynaptic receptors
Antidepressants dampen down HPA axis hyperactivity
Increased hippocampal glucocorticoid receptor expression
SSRIs may promote neurogenesis
212
Exaples of TCS
SSRIS
MAIO
NA-selective reuptake inhibitors
```
Tricyclic antidepressants (TCA), block reuptake of NA and 5-HT (imipramine)
Selective serotonin (5-HT) reuptake inhibitors (SSRI) (fluoxetine)
NA-selective reuptake inhibitors (reboxetine)
Monoamine oxidase inhibitors (MAOI), block degradation of NA and 5-HT (phenelzine)
```
All elevate monoamine levels but antidepressant effect takes several weeks
213
How does taking buspirone and ssris help anxiety (GAD) or increase Serotonin transmission
Taking buspirone, overactivates pre synaptic receptors.
Body realises there is too much activation of these receptors hence too much inhibition, body down regulate the receptors causing this inhibition, resulting in increased release overall, increased serotonin in synapse.
SSRis, stop serotonin uptake, so lots of serotonin in synapse, causes over activation or pre and post synaptic serotonin receptors, causes over inhibition of further serotonin release. Body then realises this increased activation of receptors, down regulates pre synaptic, therefore reduced inhibiton of serotonin release. also down regulates post synaptic, but overall effect is enhancement, as 2 things increase transmission (fewer 5ht1a receptors, and 5HT reuptake inhibited, and only 1 thing decreases serotonin transmission, fewer post synaptic 5HT receptors).
214
candidate genes of SCZ
COMT
DIS1
GRM3
215
what is ketamine
NMDA receptor antagonists
216
4 key typical antipsychotics
Chlorpromazine
• Fluphenazine
• Haloperidol
• Flupentixol
217
atypical antipsychotics
Clozapine
• Olanzapine
• Risperidone
• Aripiprazole
218
what are the side effects of scz drugs
```
Extra-pyramidal side effects
• Antipsychotic malignant syndrome
• Increased prolactin secretion
• Weight gain
• Sedation
• Hypotension
• Anticholinergic effects
• BONUS: Clozapine can cause agranulocytosis (low WBC)
in 1% of patients
```
219
Diff between typical and atypical scz drugs
```
Typicals
• Also known as ‘first generation’
• First developed in the 1950s
• Mainly antagonise D2
receptors
```
```
Atypicals
• Also known as ‘second
generation’
• First developed in the 1980s
• Mainly antagonise D2 and 5-HT2A
receptors
```
220
What promoters to integrate GFP
CMV/CAG all neuorne and glial cells
Gfap glial only
hSYN neurones only
CamKII excitatory neurones only
221
Describe how cre lox is expressed
Have mouse expressing lox site
Have mouse with cre expressing gene
Lox p site between stop codon then GFP protein after stop codon
Cre enzyme removes stop codon so GFP protein can be expressed in neuronal cells only
222
What are the binding sites if gabaA
2 binding sites between alpha and gamma
Benzodiazepine binding sites between alpha and gala
Channel modulator is inside ( alchohil and GA)
223
What pathway produces prolactin
Tuberohypophysealbpathway
224
Describe maternal changes in pregnancy
Increased CO
Increased blood pressure
Smooth muscle dilation causes constipation and reduce blood protein levels because increase filtration
Deeper and faster breath
Increase rbc production
Increase insulin and glucose levels
Uterus enlarges -hypertrophy or hyperplasia in response to oestrogen. Cells grow in spiral around uterus to help push baby out.
Thorax and run cage Antomy changes
Increase transferrin and clotting factors
Increased na retentjon hence increase water reabsorption and plasma volume, can result in oedema. E2 and P act on renin angiotensin system causing sodium retentjon
225
What enzyme converts testosterone into dihydrosterone
5alpha reductase
226
What enzyme converts testosterone and dihydrosterone into oestrogens
Aromatase
227
What enzyme converts testosterone into dihydrosterone
5alpha reductase
228
What enzyme converts testosterone and dihydrosterone into oestrogens
Aromatase
229
What enzyme converts progesterones into aldosterones
21 hydroxylase
230
What hormones do Sertoli vs leydig cells produce
Sertoli cells produce amh
| Leydig cells produce testosterone
231
Describe the structure of POLG
one catalytic subunit (POLgA)
2 accessory subunits POLgB
POLgA proof reads newly synthesised dna
POLgB enhances interactions with dna template and increases activity and processivity of POLgA
