23/03 Flashcards
Glycolysis
Metabolic Pathway that converts Glucose into Pyruvate
Pyruvate is utilised to generate more ATP via the Krebs cycle
Energy returns from one molecule of glucose aerobic and anaerobic
Anaerobic respiration (glycolysis only): - yielding 2 ATP
Aerobic respiration: yielding 30-32 ATP*
Three ketone bodies
When body breaks down fat
Acetoacetate
Beta-hydroxybutyrate
Acetone
Cori
ANAEROBIC
A metabolic pathway that recycles lactate produced by muscles during anaerobic glycolysis, converting it back into glucose in the liver.
Muscles (producing lactate), liver (converting lactate to glucose), and the bloodstream (transporting lactate and glucose)
Citric acid / Krebs cycle
AEROBIC
A series of biochemical reactions that oxidize acetyl-CoA derived from carbohydrates, fats, and proteins, releasing energy in the form of ATP, NADH, and FADH2.
Acetyl co-A –> C02
Acetyl-CoA combines with oxaloacetate to form citrate, initiating the cycle.
Through a series of oxidation reactions, citrate is converted back to oxaloacetate.
Main products: carbon dioxide, ATP,NADH and FADH2.
Main enzyme dehydrogenases
8 enzymatic reactions
In mitochondria
Oxidative phosphorylation
making ATP by donating electrons in the electron transport chain
Stops with
NADH
FADH2
(generated in citric acid cycle, FA oxidation, glycolysis)
What makes glutamate unique?
Only AA that doesnt have to transfer amine group
Undergoes oxidative deamination
(removed hydrogens and amino group)
» in liver mitochondria
» goes into ureic cycle
Glucogenic AA
Alanine
Glycine
Phenyl (both)
Ketogenic AA
Leucine
Lysine
Phenyl (both)
Urea cycle
In liver
Ammonia –> Urea
PMS pathophysiology
Serum concentrations of oestrogen/progesterone are SAME but people are more sensitive to cyclical changes –
altered sensitivity to oestogen, progesterone, allopregnanolone
Luteal phase –> high levels of progesterone and allopregnanolone –> changes in conformation of the GABA-A receptor –> irritability, mood swings, anxiety, sedation
Changing hormone levels may impact the serotonin system
SSRIs may also alter Allopregnanolone levels
Allopregnanolone
Metabolite of progesterone, that acts as a positive allosteric modulator of the GABA-A receptor, influencing mood, anxiety, and stress responses
GABA is the primary inhibitory neurotransmitter in the CNS –> reduces neuronal excitability, promoting calmness and inhibiting overstimulation (anxiolytic)
PMS treatment
1st line
Lifestyle and Vit B6
COCP
Continous/ luteal phase (15-28) low dose SSRI (citalopram)
2nd line
HRT-100mcgpatched plus mc prog
higher SSRI
3rd line
GnRH plus addback HRT
4th
Hysterectomy +/- HRT
Why vit B 6 in PMS
Neurotrasmitter production of both serotonin and gamma-aminobutyric acid
SSRI MOA
Blocks reabsorption of serotonin into nerve 1 so that more serotonin stays around to fill up nerve 2s receptors
Potent inhibitors of the serotonin (5-HT)-uptake
Therefore increases availability/activity of serotonin
Serotonin important in mood regulation, “happy hormone”
Side effects: nausea, diarrhoea, constipation, sleep disturbances, sexual dysfunction, agitation, anxiety
Contraindicated in QT-interval prolongation (citalopram), poorly controlled epilepsy
Treating PMS with progesterone or progestogens is not appropriate - worsening of symptoms: why?
Synthetic progestin compounds can be metabolized to Allo or similar neuroactive compounds that bind the GABAA receptor and alter the subunit composition, with resultant symptoms in susceptible individuals
Fibroids cytokine involved
TGF-β regulates the expression and growth of uterine smooth muscle and UFs.
Fibroids classification
Submucosal group
type 0: pedunculated intracavitary
type 1: <50% intramural
type 2: ≥50% intramural
Other group
type 3: 100% intramural; contacts endometrium
type 4: intramural
type 5: subserosal ≥50% intramural
type 6: subserosal <50% intramural
type 7: subserosal pedunculated
type 8: other, e.g. cervical, parasitic
Hybrid leiomyoma group
leiomyomas that impact both the endometrium and serosa
» two numbers listed separately separated by a hyphen with the first number indicating the endometrial relationship and the second number the serosal relationship
» 2-5
» submucosal / subserosal
Fibroid degen
Hyaline - most common
homogeneous eosinophilic bands or plaques in the extracellular space, which represent the accumulation of proteinaceous tissue
Myxomatous - gelatinous materia
Cystic
Extreme sequel of oedema.
Red - pregnancy
Fibroid cutoff for iud
<3cm
Hemorrhagic cyst on USS
Lace-like reticular echoes or an intracystic solid clot “spider’s web”
Endometroimas on USS
Complex mass on ultrasound, described as having “ground glass” internal echoes
IOTA M features
irregular solid tumour
irregular multilocular-solid mass >10 cm in diameter
≥4 papillary structures
ascites
high Doppler signal (colour score 4)
IOTA B features
unilocular cyst
smooth multilocular tumour <10 cm
solid components <7 mm in diameter
presence of acoustic shadows
no detectable Doppler signal
IOTA rules
When the rules can be applied (~75% of masses), there is a sensitivity of ~90% and a specificity of ~95%, which is similar to subjective expert evaluation.
If one or more M features are present in absence of B feature(s), the mass is classified as malignant
If one or more B features are present in absence of M feature(s), the mass is classified as benign
If both M features and B features are present, or if no B or M features are present, the result is inconclusive and a second stage test is recommended
Theca lutein
Grapes - like wine
Glass of the theca lutein pls
Luteinized follicle cysts that form as a result of overstimulation in elevated human chorionic gonadotropin (hCG) levels
Occur in pregnant women, women with GTD, multiple gestation, ovarian hyperstimulation
Almost always bilateral
Serous and mucinous cystadenomas
Epithelial cell benign tumours
Mucinous cystadenomas tend to be larger than serous cystadenomas
Mucinous - multilocular with numerous thin septations
Serous - usually appear as large unilocular anechoic cyst
Diameter 10 cm on average
Dermoid cyst vs mature cystic teratoma
Ovarian dermoid cyst = purely ectodermal in origin, so contains dermal and epidermal elements (hence the name)
Ovarian mature cystic teratoma = tissue can arise from any of the three germ cell layers (mesoderm, endoderm and ectoderm). Normally 2 of the 3 are seen.
Functional hypothalamic amenorrhoea
Low oestrogen Low FSH Low LH
Normal/ low LH:FSH ratio
Normal testosterone
Pathophysiology dysmenorrhea
Elevated prostaglandin F2 alpha (PGF2 α) and E2 (PGE2) levels in the secretory endometrium
Results in uterine hypercontractility, therefore severe cramping
During menses, these contractions decrease uterine blood flow and cause ischemia and sensitization of pain fibers
COCP and dysmenorrhea
> > Suppress ovulation and endometrial proliferation
> > Progestin component also blocks the production of the precursor to prostaglandin formation
> > Thinned endometrium then contains less arachidonic acid (precursor to prostaglandins)
> > Less uterine contractility and resultant pain with menses
Adenomyosis
DEPTH OF AT least 2.5 mm from the basalis layer of the endometrium
The presence of endometrial glands and stroma in the myometrium defines adenomyosis
Adenomyosis on uss
Asymmetrically enlarged, globular uterus
Posterior wall is usually involved more than the anterior wall
Irregular endometrial–myometrial junction, tiny (1-5 mm) anechoic myometrial and subendometrial cysts (specific sign) - reflecting glands filled with fluid
Prostaglandin level in endometriosis implants is significantly higher than in normal tissue
Aromatase inhibitors
Aromatase inhibitors (anastrozole, letrozole, exemestane)
Inhibits conversion of androgens into estrogens by aromatase
Aromatase enzymes available in ovary, adipose tissue, liver, muscle, brain, skin, bone, endometrium, and breast tissue
Endometriosis (oestrogen-dependent disease) - refractory to other medical options
Indications:
Endometrial Ca
Infertility/ovulation induction
Hormone-dependent breast cancer (post-menopausal)
CI
Susceptibility to osteoporosis
SE
Menopausal sx
Alopecia; arthralgia; bone fracture; depression; hot flush; hypercholesterolaemia; hypertension; malaise; myalgia; osteoporosis; vaginal haemorrhage
hepatic porphyria and hormones
(Acute intermittent porphyria)
Acute intermittent porphyria is a
rare disorder characterised by acute attacks often precipitated by drugs.
Estrogen and progestogen
have been implicated.
Combined hormonal contraception is shown to reduce attacks for some women.
Natural fluctuations in estrogen and progesterone appear to be associated with acute attacks more often than
exogenous hormones.
Only in UKMEC for EC
UKMEC 1 Cu-IUD
2 for both PO options
Spironolactone
Reduces testosterone level by direct inhibition of 17α-hydroxylase enzyme.
Also inhibits 5α-reductase, which is the enzyme that converts testosterone to the more potent DHT hormone.
Indications:
Anti-androgens could be considered to treat hirsutism in women with PCOS, if there is a suboptimal response after a minimum of six months of COCP and/or cosmetic therapy
Cautions
Also aldosterone antagonist (antimineralocorticoid) disrupting the sodium/potassium balance
Hyperkalaemia risk
SE
AKI
Chronic use - metabolic acidosis (aldosterone antagonist)
Metformin
Mechanism of action
Insulin sensitiser
Inhibits production of hepatic glucose, decreases lipid synthesis, increases fatty acid oxidation and inhibits gluconeogenesis - decreased circulating insulin and glucose
Enhances insulin sensitivity at the cellular level and also appears to have direct effects within the ovary
Indications
Considered in adults with PCOS and a BMI for anthropometric, and metabolic outcomes including insulin resistance, glucose, and lipid profiles (off-label use)
Reduces serum androgen levels, improves insulin sensitivity, restores menstrual cyclicity, and triggering ovulation
SE
Nausea, vomiting, abdominal pain, diarrhoea, dizziness and unusual tiredness
Case control vs cohort
case control
Starting point = outcome - go back to look at exposures.
start by collecting cases (e.g. rare disease) - with the outcome then look back at exposure.
Find RF
Adv: rare, correlation, cheap, quick
Disadv: confounding (cant say causation)
contrOl
O for odds
O for outcome (start with outcome)
cohort
Start with exposure (RF) and follow over time see what outcomes come
Adv: rare exposures, multiple outcomes of interest, ethical
Dis: time and cost, stronger than c-c
CohoRt
R for Risk
R for RF/ exposure start with
How to work out TP and TN
True Positives (TP) = Sensitivity * Prevalence * Total Population
True Negatives (TN) = Specificity * Prevalence * Total Population
Positive Predictive Value & Disease Prevalence
If you have prev, spec and sens
(1) Work out TP from (make up total pop)
Sensitivity * Prevalence * Total Population
(2) Work out TN from Sensitivity * Prevalence * Total Population (use above made up total pop)
(3) Work out FP
Prevalence - (Prevalence * Total Population) - TN
(4) Work out PPV
(TP +FP) / TP
CHC family hx of VTE UKMEC
(i) First-degree relative age
<45 years
3
(ii) First-degree relative age
≥45 years
2
When does it matter if History (≥5 years ago) of migraine with aura, any age
Only CHC when goes from 4 to 3
Rest of PO methods are 2 for both
Smoking and UKMEC
Only really matters in CHC methods
<35 all UKMEC 2
>= 35
(i) <15 cigarettes/day 3
(ii) ≥15 cigarettes/day 4
(iii) Stopped smoking <1 year 3
(iv) Stopped smoking ≥1 year 2
LNG release iuds
Total LNG content
Initial release rate/day
End of license release rate/day
52 mg
20 mcg
8.6-9 mcg
19.5 mg
17.5 mcg
7.4 mcg after 5yr
13.5 mg
14 mcg (for the first 24 days)
5 mcg after 3 years
chc why need to check tft
Oestrogen may reduce thyroid levels by increasing thyroid binding globulin and increasing thyroxine requirements. Thyroid levels should be checked within 6 weeks of initiating combined hormonal contraception.
