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
What are effects of impaired renal function on drugs?
1) decreased clearance - increased sensitivity/higher chance of toxicity
2) decreased protein binding
3) decreased efficacy e.g. UTI antibiotics/diuretics
4) worsening of existing condition, e.g. steroids, cause fluid retention
Dose adjusment is essential for:
o Drugs with at least 50% renal clearance
o Drugs with low therapeutic index
What effect do NSAIDs have on Autoregulation of the Glomerular Filtration Rate?
NSAIDs block production of vasodilatory prostaglandins
These usually act to dilate the afferent arteriole
If perfusion pressure drops, e.g. with haemorrhage, the kidney cannot dilate the afferent arteriole
Pressure drops in the glomerulus and there is decreased filtration
What effect do ACEi have on Autoregulation of the Glomerular Filtration Rate?
ANG II normally constricts the efferent arteriole
With ACEi, the body is unable to increase ANG II in response to increased vasodilatory prostaglandins
o Cannot maintain pressure in the glomerulus
o Perfusion pressure drops
frequently nephroprotective in renal disease especially if proteinuria
However potential to cause acute drop in GFR if dehydrated or in patient with renal artery stenosis. Renal function may rapidly drop in this setting
What is the main site of nephrotoxicity?
PCT
What is the effect of sympathetic stimulation on GFR?
reduces GFR by constricting the afferent arteriole
What happens to osmolality along the PCT?
does not change because water follows sodium
Minimum daily urine production
400ml
Maximum daily urine production
12L
Waste products excreted /day
600 mOsm
Normal urine production
in an adult human under no particular physiological or pathophysiological stress, about 100 ml of glomerular filtrate is generated from plasma each minute, 99 ml of which is reabsorbed, leaving a urinary volume of 1 ml/min.
0.5-1ml/kg/hr = average adult patient.
A disabled person:
“...has a physical or mental impairment and the impairment has a substantial and long-term adverse effect on his or her ability to carry out normal day-to-day activities.”
What is the combined oral contraceptive pill?
consists of oestrogen and progesterone in varying concentrations
Describe 3 major actions of the combined oral contraceptive pill
1) inhibit ovulation - oestrogen/progesterone both have a negative feedback effect on gonadotropin release from the pituitary
2) thicken cervical mucous to prevent sperm penetration - progesterone alters cervical mucous consistency
3) prevent implantation - oestrogen and progesterone result in inadequate endometrial proliferation
Describe the sequence of events that occur in the ovary during the follicular phase.
groups of follicles in the ovary are stimulated to develop under the influence of FSH
One of the follicles starts to grow rapidly and becomes the dominant follicle. As this follicle develops, it secretes increasing amounts of oestrogen
High oestrogen levels feed back positively to the anterior pituitary to stimulate continuous FSH/LH release
Describe the sequence of events that occur in the ovary during ovulation.
14 days before menstruation a surge of LH triggers rupture of the dominant follicle and release of the secondary oocyte
Describe the sequence of events that occur in the ovary during the luteal phase.
the remaining granulosa and theca cells collapse to form the corpus luteum, which secretes predominantly progesterone and some oestrogen
Define follicular atresia
phenomenon that most follicles do not fully mature but degenerate
Define secondary follicle
a follicle in which the fluid filled antrum has formed
define zona pellucida
glycoprotein coat that forms around the oocyte as follicles mature
What is mumps and what organs does it affect?
mumps is a viral infection that particularly affects the salivary glands and the testes
At the testis, what is the difference between the tunica vaginalis and tunica albuginea?
tunica albuginea is the connective tissue capsule of the testes
tunica vaginalis is the serous membrane that invests the testes
What two cell populations are found in the seminiferous tubules of the testes?
Sertoli cells and spermatogenic cells
What is the function of leydig cells and what controls their function?
Secrete testosterone, controlled by LH from the anterior pituitary
androgen binding protein
secreted by sertoli cells
binds to testosterone and keeps its concentration high in the seminiferous tubules
What is oligospermia?
fewer than 10 million spermatozoa per millilitre
Which segments of the spinal cord receive sensory input from the bladder?
T10-L2 and S2-S4
These segments also supply output to the bladder
what is prostate-specific antigen?
protein produced by prostatic epithelial cells
Give 4 situations in which serum PSA might be raised
BPH
prostate cancer
recent ejactulation
prostatitis
How would you distinguish between BPH and prostatic carcinoma on a PR exam?
BPH is diffuse, smooth and firm
cancer is irregular in contour and heterogenous in texture
What is the rectovesical pouch and is it palpable on PR exam?
most inferior part of the peritoneum in males
too far from the anal margin to palpate in males
rectouterine pouch is more inferior and palpable in females
Which features are normal on PR exam?
rubbery consistency
longitudinal groove
mobile rectal mucosa
Why are U&Es checked with suspected BPH?
BPH can cause BOO and impair urinary flow, leading to renal failure
What are the parts of the male urethra and their approximate lenghts?
prostatic urethra - 3-4 cm
membranous urethra - 1-2 cm
spongy urethra - 15 cm
Which part of the urethra does the EUS surround and what is its nerve supply?
membranous urethra, supplied by pudendal nerve
Which muscle helps expel the last drops of urine?
bulbospongiosus muscle
Which nerves innervate the blood vessels of the corpora cavernosa/spongiosum and are responsible for initiating erection?
pelvic splanchnic nerves (parasympathetic nerves)
What prevents ejaculate from entering the bladder?
internal (vesical) sphincter
What is the appearance of prostatic tissue under a light microscope?
glandular tissue with simple columnar epithelium embedded in a fibromuscular stroma
What are amyloid bodies?
eosinophilic bodies in the lumen of prostatic glands
What type of nerve fibres innervates the smooth muscle of the prostate that contracts at ejaculation?
sympathetic fibres
Where do the kidneys lie?
retroperitoneal
T12-L3 (variable)
partly protected by 11-12th ribs
Atrial Natriuretic Peptide
hormone release from the atria when blood volume is high.
The increased venous return stretches the walls of the atria, and release ANP, which is responsible for:
Dilation of afferent arterioles & constriction of efferent arterioles, thus ↑ GFR.
↓ Na+ reabsorption in the tubules, increasing urine output and reducing blood volume/pressure.
Typical Clinical Features of CKD
1) elevated serum creatinine
2) elevated serum urea
3) anaemia (decreased EPO causes reduced maturation of the RBCs, and a subsequent drop in the level of serum haemoglobin)
4) hypertension (due to fluid retention)
5) proteinuria
Causes of acute kidney injury
1) pre-renal - e.g. renal artery stenosis
2) renal parenchhymal - e.g. tubular/glomerular disease
3) post-renal - e.g. bladder outlet obstruction (BPH, renal stones, tumours)
CKD progression
nephron loss causes initial compensatory hyperfiltration at remaining nephrons. This causes proteinuria and nephron damage.
Protein reuptake in tubules causes fibrosis and inflammation. Progressive deteriotation in function results in decreased GFR
Hydronephrosis
dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to
obstruction to the outflow of urine.
DIALYSIS
process of removing, by artificial means, excess water, solutes and toxins from the blood in those whose kidneys have lost the ability to perform those functions
Which diuretics increase calcium excretion?
loop diuretics
Which diuretics decrease calcium excretion?
thiazide diuretics
What artery supplies the pelvic floor muscles?
internal iliac
What embryological structure divides into 2, to form the bladder?
cloaca