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Question 1

Polycystic ovary syndrome (PCOS)

Answer 1

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

Question 2

Transgender

Answer 2

someone whose gender is different from their assigned sex at birth

Question 3

What is the major source of mucus found in the vagina?

Answer 3

Glands of the uterine cervix

Question 4

What is the character and functional significance of the mucus at midcycle?

Answer 4

It is viscous / stretchy (0.5) and can be easily penetrated by sperm (0.5)

Question 5

Why might the gynaecologist inspect the mucus under a microscope?

Answer 5

He is looking for motile sperm to assess the husband’s fertility

Question 6

Give two mechanisms that negatively control FSH production in the natural female
cycle

Answer 6

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)

Question 7

What barriers must the sperm penetrate to fertilise an oocyte?

Answer 7

Cumulus oophorus or corona radiata (1)
Zona pellucida (1)
Oocyte plasma membrane (1)

Question 8

What are the two blocks to polyspermy and how do they work?

Answer 8

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)

Question 9

What is the significance of the blocks to polyspermy?

Answer 9

Defence mechanism to prevent multiple sperm entering a single oocyte and causing too many
copies of chromosomes from the male parent

Question 10

when does implantation occur?

Answer 10

day 7-12 after fertilisation

Question 11

When does the pre-embryo enter the uterine cavity?

Answer 11

end of week 1

Question 12

What does mild hyperkalaemia indicate?

Answer 12

Chronic renal failure. Significant hyperkalaemia indicates acute renal failure

Question 13

Define chronic renal failure

Answer 13

loss of renal function which is slowly progressive, often longstanding, and usually associated with irreversible structural damage

Question 14

What is the most likely cause of chronic renal failure in a 72-year-old male in Scotland?

Answer 14

widespread vascular disease and atheroma

Question 15

Why is serum creatinine a good marker of GFR?

Answer 15

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

Question 16

What happens to concentration of serum creatinine with a 50% reduction in GFR?

Answer 16

concentration of serum creatinine will double, because the concentration in blood is directly proportional to the total GFR

Question 17

Explain how normocytic, normochormic anaemia comes about

Answer 17

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

Question 18

Explain how CKD causes hypocalcaemia.

Answer 18

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

Question 19

What tests would you carry out to determine if a patient has CKD? What findings do you expect?

Answer 19

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

Question 20

What is renal osteodystrophy?

Answer 20

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.

Question 21

What is the response of the Juxta-glomerular apparatus: to increased GFR?

Answer 21

Macula densa senses increased tubular flow

MD cells release adenosine, which causes vasoconstriction of the afferent arteriole, decreasing GFR

Question 22

What is the response of the Juxta-glomerular apparatus: to decreased GFR?

Answer 22

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

Question 23

What variables does eGFR correct for?

Answer 23

sex, age and ethnicity

Question 24

Limitations of eGFR

Answer 24

not accurate >60ml/min
not accurate in people <18

Inverse relationship leads to:

1. Slow recognition of loss of the first 70% of kidney function (look at shape of the graph!)
2. 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

Question 25

For someone with higher muscle mass than usual, eGFR will be ..

Answer 25

eGFR will be an underestimate of true function. There will be more creatinine detected in the urine because there is more being produced

Question 26

For someone with lower muscle mass than usual, eGFR will be ..

Answer 26

eGFR will be an overestimate of true function. There will be less creatinine detected in the urine because there is less being produced

Question 27

What are kidney injury / disease defined by?

Answer 27

o reduced eGFR | o detection and quantification of urine protein +/- blood

Question 28

Causes of kidney injury/disease (3 classes)

Answer 28

1) ‘pre-renal’ 2) ‘obstructive’ 3) ‘renal parenchymal’ combinations are also common

Question 29

What causes high anion gap acidosis?

Answer 29

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

Question 30

What causes normal anion gap acidosis?

Answer 30

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

Question 31

What is the effect of blood pH on calcium levels?

Answer 31

acute alkalosis increases binding of Ca2+ to albumin. | This causes a fall in ionised Ca2+ and therefore tetany

Question 32

Describe the process of Hyperacute transplant rejection

Answer 32

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

Question 33

Describe the process of acute transplant rejection

Answer 33

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

Question 34

What are effects of impaired renal function on drugs?

Answer 34

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

Question 35

What effect do NSAIDs have on Autoregulation of the Glomerular Filtration Rate?

Answer 35

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

Question 36

What effect do ACEi have on Autoregulation of the Glomerular Filtration Rate?

Answer 36

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

Question 37

What is the main site of nephrotoxicity?

Answer 37

PCT

Question 38

What is the effect of sympathetic stimulation on GFR?

Answer 38

reduces GFR by constricting the afferent arteriole

Question 39

What happens to osmolality along the PCT?

Answer 39

does not change because water follows sodium

Question 40

Minimum daily urine production

Answer 40

400ml

Question 41

Maximum daily urine production

Answer 41

12L

Question 42

Waste products excreted /day

Answer 42

600 mOsm

Question 43

Normal urine production

Answer 43

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.

Question 44

A disabled person:

Answer 44

``` “...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.” ```

Question 45

What is the combined oral contraceptive pill?

Answer 45

consists of oestrogen and progesterone in varying concentrations

Question 46

Describe 3 major actions of the combined oral contraceptive pill

Answer 46

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

Question 47

Describe the sequence of events that occur in the ovary during the follicular phase.

Answer 47

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

Question 48

Describe the sequence of events that occur in the ovary during ovulation.

Answer 48

14 days before menstruation a surge of LH triggers rupture of the dominant follicle and release of the secondary oocyte

Question 49

Describe the sequence of events that occur in the ovary during the luteal phase.

Answer 49

the remaining granulosa and theca cells collapse to form the corpus luteum, which secretes predominantly progesterone and some oestrogen

Question 50

Define follicular atresia

Answer 50

phenomenon that most follicles do not fully mature but degenerate

Question 51

Define secondary follicle

Answer 51

a follicle in which the fluid filled antrum has formed

Question 52

define zona pellucida

Answer 52

glycoprotein coat that forms around the oocyte as follicles mature

Question 53

What is mumps and what organs does it affect?

Answer 53

mumps is a viral infection that particularly affects the salivary glands and the testes

Question 54

At the testis, what is the difference between the tunica vaginalis and tunica albuginea?

Answer 54

tunica albuginea is the connective tissue capsule of the testes tunica vaginalis is the serous membrane that invests the testes

Question 55

What two cell populations are found in the seminiferous tubules of the testes?

Answer 55

Sertoli cells and spermatogenic cells

Question 56

What is the function of leydig cells and what controls their function?

Answer 56

Secrete testosterone, controlled by LH from the anterior pituitary

Question 57

androgen binding protein

Answer 57

secreted by sertoli cells | binds to testosterone and keeps its concentration high in the seminiferous tubules

Question 58

What is oligospermia?

Answer 58

fewer than 10 million spermatozoa per millilitre

Question 59

Which segments of the spinal cord receive sensory input from the bladder?

Answer 59

T10-L2 and S2-S4 These segments also supply output to the bladder

Question 60

what is prostate-specific antigen?

Answer 60

protein produced by prostatic epithelial cells

Question 61

Give 4 situations in which serum PSA might be raised

Answer 61

BPH prostate cancer recent ejactulation prostatitis

Question 62

How would you distinguish between BPH and prostatic carcinoma on a PR exam?

Answer 62

BPH is diffuse, smooth and firm cancer is irregular in contour and heterogenous in texture

Question 63

What is the rectovesical pouch and is it palpable on PR exam?

Answer 63

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

Question 64

Which features are normal on PR exam?

Answer 64

rubbery consistency longitudinal groove mobile rectal mucosa

Question 65

Why are U&Es checked with suspected BPH?

Answer 65

BPH can cause BOO and impair urinary flow, leading to renal failure

Question 66

What are the parts of the male urethra and their approximate lenghts?

Answer 66

prostatic urethra - 3-4 cm membranous urethra - 1-2 cm spongy urethra - 15 cm

Question 67

Which part of the urethra does the EUS surround and what is its nerve supply?

Answer 67

membranous urethra, supplied by pudendal nerve

Question 68

Which muscle helps expel the last drops of urine?

Answer 68

bulbospongiosus muscle

Question 69

Which nerves innervate the blood vessels of the corpora cavernosa/spongiosum and are responsible for initiating erection?

Answer 69

pelvic splanchnic nerves (parasympathetic nerves)

Question 70

What prevents ejaculate from entering the bladder?

Answer 70

internal (vesical) sphincter

Question 71

What is the appearance of prostatic tissue under a light microscope?

Answer 71

glandular tissue with simple columnar epithelium embedded in a fibromuscular stroma

Question 72

What are amyloid bodies?

Answer 72

eosinophilic bodies in the lumen of prostatic glands

Question 73

What type of nerve fibres innervates the smooth muscle of the prostate that contracts at ejaculation?

Answer 73

sympathetic fibres

Question 74

Where do the kidneys lie?

Answer 74

retroperitoneal T12-L3 (variable) partly protected by 11-12th ribs

Question 75

Atrial Natriuretic Peptide

Answer 75

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.

Question 76

Typical Clinical Features of CKD

Answer 76

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

Question 77

Causes of acute kidney injury

Answer 77

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)

Question 78

CKD progression

Answer 78

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

Question 79

Hydronephrosis

Answer 79

dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine.

Question 80

DIALYSIS

Answer 80

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

Question 81

Which diuretics increase calcium excretion?

Answer 81

loop diuretics

Question 82

Which diuretics decrease calcium excretion?

Answer 82

thiazide diuretics

Question 83

What artery supplies the pelvic floor muscles?

Answer 83

internal iliac

Question 84

What embryological structure divides into 2, to form the bladder?

Answer 84

cloaca