2 Flashcards
Polycystic ovary syndrome (PCOS)
Signs and symptoms of PCOS include:
- irregular or no menstrual periods
- high androgen levels –> hirsutism, acne
- ovarian cysts
- heavy periods
- pelvic pain
- fertility problems
PCOS can result from abnormal function of the hypothalamic-pituitary-ovarian (HPO) axis.
LH/FSH secretion is ‘out of balance’.
Increase LH leads to increased androgen
production
o Interconversion of hormones
o Impacts adipose tissue –> insulin resistance
Transgender
someone whose gender is different from their assigned sex at birth
What is the major source of mucus found in the vagina?
Glands of the uterine cervix
What is the character and functional significance of the mucus at midcycle?
It is viscous / stretchy (0.5) and can be easily penetrated by sperm (0.5)
Why might the gynaecologist inspect the mucus under a microscope?
He is looking for motile sperm to assess the husband’s fertility
Give two mechanisms that negatively control FSH production in the natural female
cycle
Negative feedback by oestrogen produced as the follicles develop causes a decrease in FSH due
to inhibition of GnRH (0.5)
Inhibin down regulating FSH synthesis and secretion(0.5)
What barriers must the sperm penetrate to fertilise an oocyte?
Cumulus oophorus or corona radiata (1)
Zona pellucida (1)
Oocyte plasma membrane (1)
What are the two blocks to polyspermy and how do they work?
Fast block (0.5) – rapid depolarisation of the egg membrane (0.5), lasts around a minute (0.5)
Slow block (0.5)– begins with a wave of calcium from site of sperm egg fusion (0.5), cortical reaction occurs (0.5) cortical granules release proteases (0.5) which hydrolyse sperm receptor molecules in the zona pellucida (0.5)
What is the significance of the blocks to polyspermy?
Defence mechanism to prevent multiple sperm entering a single oocyte and causing too many
copies of chromosomes from the male parent
when does implantation occur?
day 7-12 after fertilisation
When does the pre-embryo enter the uterine cavity?
end of week 1
What does mild hyperkalaemia indicate?
Chronic renal failure. Significant hyperkalaemia indicates acute renal failure
Define chronic renal failure
loss of renal function which is slowly progressive, often longstanding, and usually associated with irreversible structural damage
What is the most likely cause of chronic renal failure in a 72-year-old male in Scotland?
widespread vascular disease and atheroma
Why is serum creatinine a good marker of GFR?
creatinine is produced from skeletal muscle at a relatively constant rate.
It is freely filtered at the glomeruli, and neither secreted nor reabsorbed to a significant degree.
Therefore, the amount filtered per unit time will equal the amount excreted in urine for the same unit time.
GFR = urine concentration x urine flow rate / plasma concentration of creatinine
What happens to concentration of serum creatinine with a 50% reduction in GFR?
concentration of serum creatinine will double, because the concentration in blood is directly proportional to the total GFR
Explain how normocytic, normochormic anaemia comes about
Fall in EPO production with chronic renal damage.
EPO is made in the renl tubular cells in response to hypoxia. Normally this will ensure that there is appropriate erythropoiesis in the bone marrow.
In CKD, insufficient EPO production results in decreased number of RBC of normal size and haemoglobin content
Explain how CKD causes hypocalcaemia.
Caused by two mechanisms:
1) defective hydroxylation of 25-hydroxycholecalciferol, leading to reduced vitamin D production and thereby reduced Ca absorption in the gut
2) as a consequence of elevated phosphate levels. Decreased GFR = decreased phosphate excretion. Blood calcium levels are lowered because calcium and phosphate levels need to be maintained within a narrow range
What tests would you carry out to determine if a patient has CKD? What findings do you expect?
1) blood test
2) BP (lying and standing) - will be significantly raised
3) urinalysis - microalbuminaemia, haematuria, proteinuria, glycosuria
4) abdominal ultrasound - small shrunken kidneys, with or without obstruction
What is renal osteodystrophy?
bone disease due to a combination of disturbed vitamin D metabolism and secondary hyperparathyroidism found in patients with longstanding CKD.
Presents clinically with bone pain and fracture.
What is the response of the Juxta-glomerular apparatus: to increased GFR?
Macula densa senses increased tubular flow
MD cells release adenosine, which causes vasoconstriction of the afferent arteriole, decreasing GFR
What is the response of the Juxta-glomerular apparatus: to decreased GFR?
Decreased luminal flow is detected by the macula densa cells
MD cells stimulate granular cells are to secrete renin
o Results in RAAS activation
ANG II causes vasoconstriction of the efferent arteriole = increases glomerular filtration pressure. This preserves glomerular filtration even though the blood flow to the kidneys has decreased
Aldosterone increases Na reabsoprtion, and H2O, increasing blood volume
What variables does eGFR correct for?
sex, age and ethnicity
Limitations of eGFR
not accurate >60ml/min
not accurate in people <18
Inverse relationship leads to:
- Slow recognition of loss of the first 70% of kidney function (look at shape of the graph!)
- Surprise at the sudden rise in creatinine
Effect of muscle mass leads to:
1. Overestimation of function in women
2. Overestimation of function in the elderly
3. Overestimation in other low muscle mass groups e.g. Amputees, para/quadriplegics, rheumatoid
arthritis
For someone with higher muscle mass than usual, eGFR will be ..
eGFR will be an underestimate of true function.
There will be more creatinine detected in the urine because there is more being produced
For someone with lower muscle mass than usual, eGFR will be ..
eGFR will be an overestimate of true function. There will be less creatinine detected in the urine because there is less being produced
What are kidney injury / disease defined by?
o reduced eGFR
o detection and quantification of urine protein +/- blood
Causes of kidney injury/disease (3 classes)
1) ‘pre-renal’
2) ‘obstructive’
3) ‘renal parenchymal’
combinations are also common
What causes high anion gap acidosis?
Na - (Cl + HCO3) = nomrally 6-12 mmol/L
o Lactic acidosis
o Ketoacidosis
o Poisoning
High anion gap is caused by addition of an ORGANIC acid. H+ is buffered by bicarbonate and the remainder of the acid is not taken into account in the equation = more negative ions not accounted for = higher anion gap
What causes normal anion gap acidosis?
Diarrhoea
failure to excrete acid (type 2 renal tubular acidosis).
due to a loss of bicarbonate, which is compensated for with increased Cl- reabsorption in the kidney
NB: Beware that decreased albumin affects the anion gap
What is the effect of blood pH on calcium levels?
acute alkalosis increases binding of Ca2+ to albumin.
This causes a fall in ionised Ca2+ and therefore tetany
Describe the process of Hyperacute transplant rejection
occurs if patient has pre-formed complement fixing donor reactive antibodies.
Donor antibodies bind to the mismatched HLA antigens in the graft endothelium, which activates a complement cascade.
This results in recruitment of pro-inflammatory cytokines, which cause endothelial cell damage
MAC also causes endothelial cell damage
Recruitment of neutrophils and
Platelets are activated –> aggregate, causing thrombosis
Results in prevention of vascularisation of graft - irreversible damage from ischaemia
Describe the process of acute transplant rejection
all patients are at risk of acute rejection
Immune mediated by T-cells (cellular) and B-cells (antibodies) –> DE NOVO response
o Patient may become non-compliant with immunosuppressants or drug strategy may not be
optimum for the patient
o Immune response may be generated against the organ
