SHIT IDK YET Flashcards
process of steroidogenesis
Cholesterol is the main component, it has three 6 sided rings and one 5 sided ring. There are carbons numbered 20 to 27 on the 5 sided ring.
Progestogens are made through carbon 22 to 27 being removed. There are only 21 carbons.
Androgens are made by removing carbons 20 to 27. There are only 19 carbons.
Oestrogens are made by removing carbon 19 to 27. There are only 19 carbons.
congenital adrenal hyperplasia
- enzyme 21-hydroxylase is not functioning
- progestogens are not converted so they increase
- progestogens are converted into testosterone
- testosterone causes the wolffian ducts to develop producing male external genitalia
- as cortisol is not produced there is no negative feedback so ACTH increases which stimulates the adrenals
- more progestogens increase so more testosterone is made
- XX female with CAH has no AMH, high levels of testosterone therefore male and female internal genitalia will develop
- DHT is present, producing male external genitalia
gonadal dysgenesis
This is where sexual differentiation is incomplete so the genitalia does not develop properly.
Happens due to:
- missing SRY in male
- partial and complete deletion of second X in female
e.g. AIS, 5-α-reductase deficiency, Turner syndrome and congenital adrenal hyperplasia
5-α-reductase deficiency
- type of gonadal dysgenesis
- testosterone is made but not DHT due to absence of enzyme
- autosomal recessive disorder and can depend on inter-related marriage
features: - testes form, AMH acts, testosterone acts
- internal structures form but external do not
Extent of features depends on degree of enzyme block.
Assessment has to happen at puberty as high testosterone at the adrenarche and puberty can induce virillisation.
structure of gonadotrophins
- heterodimeric peptides
- FSH and LH have N-linked carbohydrate chains
- hCG has O-linked side chains
what hormones does the anterior pituitary gland release
- FSH
- LH
- TSH
- ACTH
- GH
- PRL
Outline the menstrual cycle, starting from the death of the CL and thus the fall in Progesterone
- Decreased Progesterone
- Leads to decreased negative feedback and the intercycle rise in FSH
- FSH causes maturation of antral follicles
- Antral follicles produce E2
- Increased E2 causes negative feedback and a fall in FSH leading to the death of all but the dominant follicle
- The dominant follicle produces high consistent E2 which becomes +Ve feedback
- LH surge
- Ovulation
- High progesterone from the CL
- Negative feedback slowly reduces gonadotrophs and P falls as the CL die
Tanner stage IV
Coarse hair across pubis (not thighs)
Increase penis width/glans
Breasts enlarge, raised areolar
Tanner stage III
Coarsening of pubic hair
Increase penis size
Enlarged breasts, mound forms
What is a non-invasive method of testing tubal patency?
Hystero Salpingo-contrast Sonogrpahy (HyCoSy)
How are spermatozoa formed in waves?
The cells remains connected to one and other by cytoplasmic bridges forming a syncytium allowing synchronous development
What are the 2 types of postcoital pills? What are their failure rates?
Levonelle - Levonorgestrel - Failure rate of 1.7%
ellaOne - ulipristal acetate - Failure rate 1.2%
What are the progesterones used in COCP?
Older (2nd gen) - Norethisterone & Levonorgestrel
Newer (3rd gen) - Desogestrel, Gestodene & Norgestamine
Latest - Drospirenone (derived from spironolactone
Outline some contraindications of the COCP
Breast cancer, Undiagnosed genital bleeding, pregnancy, <3 wks post partum, Breast feeding, HTN, migraine with aura, SLE etc…
When is the emergency contraceptive pill indicated?
Any day of the natural cycle: >21 days after pregnancy or >5 days after abortion, miscarriage, evaluation of trophoblastic disease
Any day of the cycle where contraception was compromised.
The contact of the sperm and what initiates the acrosomal reaction?
Sperm and the zona-cumulus complex
What is the corona radiata?
Innermost layers of cumulus cells in contact with the ZP
Made by granulosa cells adhering to the oocyte as it leads the follicle
What is the cortical reaction? What initiates it? What is its purpose?
- Wave of Ca2+ sweeps around the egg
- Proteases, peroxides and hyaline hardens the ZP
- Prevents polyspermy
What drug inhibits peripheral androgen receptors? What can this treat?
Cyproterone Acetate treats: Male precocious puberty, Acne, hirsutism, virilisation in women, BPH and prostate cancer
How does Danazol work? What does it treat?
Its an androgen derivative that isn’t converted into Oestrogen.
Works to reduce GnRH, LH and FSH (antioestrogenic and antiprogestogenic effects)
Treats: Gynaecomastia, Mastalgia, Benign fibrotic disease, Endometrosis, Infertility & Menorrhagia
What drugs can reduce androgen dependant prostate cancer?
Oestrogens e.g. Ethinyloestradiol, Diethylstilbestrol
Give examples of GnRH agonist analogues. What are they used for?
Buserelin, Goserelin
Cause reduced testosterone long term to treat Prostate/Breast cancer and endometriosis
Give examples of GnRH antagonists. What are they used for?
Cetrorelix & ganirelix
IVF
What are the normal and gestational Hb ranges?
Normal Hb 12-16g/dl
Pregnant Hb 10.5-13g/dl
How do glucose levels change by trimester?
1st trimester - Increase pancreatic cell number, increase maternal insulin, increase maternal reserve
2nd trimester - Glucose increased in maternal blood and actively transported into foetal circulation
3rd trimester - Placental lactogen causes insulin resistance, less maternal stores, more maternal serum glucose increases foetal glucose reserves
What are the changes in BMR during pregnancy and what is responsible for this increase?
Increase of 350 kcal/day mid gestation
Increase of 550 kcal/day late gestation
75% Uterus & Foetus
25% Maternal respiration
What is a non-hormonal medical treatment for menopause?
Clonidine - antihypertensive
Venlafaxine - SSRI which doesn’t induce CP450
Paroxetine: Tamoxifen SSRI
Alternatives to oestrogen for treating osteoporosis?
Bisphosphonates
Raloxifene
Ca2+ Vit D
Strontium
(Teriparatide, Simvastatin, leptin, phyto-oestrogens, RANKL gene manipulation & Anti-oxidants)
What is the most severe form of spina bifida?
myelomeningocele
Dose of folic acid before pregnancy?
400 micrograms/day from 3 months before conception to 3 months gestation
How does the minute volume change in pregnancy? What does this result in?
40% increase in minute volume leading to a 10% rise in arterial O2 & a 15-20% decrease in CO2
when do pregnant women get their sugar levels checked
- women who are susceptible have their levels checked at booking, 28 weeks, 34 weeks and 40 weeks
- women who are not susceptible their levels are check at 28 and 40 weeks
changes in blood in pregnancy
- plasma cell volume increases by 45%
- RBC volume increases by 18%
- as RBC does not increase as much compared the Hb concentration falls as blood is more dilute however this is normal
- non-pregnant females have Hb level os 120-160g/dl
- pregnant females have Hb levels of 105-130g/dl
what are some other problems in a mother with pre-existing diabetes
- increased risk of UTIs
- hypoglycaemia in the mother
- nephropathy (reversible)
- increased risk of retino
- GD increases risk of type 2 diabetes
- can cause poor placental function leading to intrauterine death and foetal distress
anaemia
- Hb should be investigated if it is less than 105g/dl
causes
- iron deficiency
- sickle cell or thalassaemia trait
- vitamin B12 or folate deficiency
- blood dycrasias
management
- check Hb at booking, 28 and 36 weeks
- investigate for cause of anaemia
- treat underlying cause with ferrous sulphate
- transfuse if Hb < 7g/dl or symptomatic
urinary tract infection
- increased throughout pregnancy
- relative urinary stasis as progesterone leads to smooth muscle relaxation and uterus pushes down on ureters
- there is immunosuppression to not reject the foetus
- urine should be tested at every visit
- UTI can be associated with pre-term delivery
two types of diabetes in pregnancy
- gestational diabetes is recognised for the first time after 20/40 gestation
- pre-existing insulin dependent or insulin independent diabetes mellitus this is diagnosed before 20/40 gestation
how is oxytocin used
- start with low dose of 2 to 4 MU/min then increase every 30 minutes
- most labour responds to 8-12 MU/min
- if it does not have an effect within 6-8 hours then it will not work
conditions for assisted vaginal delivery
- head has to be 0/5th or 1/5th palpable
- not a large baby
- cervix fully dilated
- membranes ruptures
- no excessive caput/moulding
- good foetal condition
- empty bladder
- suitable positon
- descent with contraction and bearing down effort
• Labour:
process of uterine contractions + cervical dilatation enabling uterus to deliver viable fetus (>24 weeks), placenta, membranes
• Diagnosed = regular, increasing painful uterine contractions bringing about progressive cervical effacement and/or dilatation
What happens to TP53 in the absence of DNA damage?
It is still made but is not activated and is therefore destroyed by proteasome
Whats (Philadelphia chromosome)
• Section of chromosome 9 gets swapped with end of chromosome 22 = tiny chromosome detected via FISH causes chronic myeloid leukemia CML
= BCR-ABL1
DNA repair defects which predispose one to cancer
- Ataxia telangiectasia
- Bloom’s syndrome
- Fanconi’s anaemia
- Li-Fraumeni syndrome
- Lynch type II
- Xeroderma pigmentosum
Molecular alterations in malignancy
- Self-sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Evasion of apoptosis
- Defects in DNA repair
- Limitless replicative potential
- Ability to invade and metastasise both intrinsic and extrinsic
- Sustained angiogenesis
