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1291 Cards in this Set

  • Front
  • Back
what is the normal total body water (TBW)?
60% of body weight (~40L for 70kg person)
what are the two components of extracellular fluid?
interstitial fluid
plasma
what is the volume of ICF in a 70kg person?
25L
what is the volume of interstitial fluid in a 70kg person?
12L
what is the volume of plasma in a 70kg person?
3L
what are the sources of fluid entering the body?
food
drink
oxidation
in what forms does fluid leave the body?
urine
stool
sweat
respiratory
what is the dominant cation in the intracellular fluid?
potassium
what are the dominant anions in the intracellular fluid?
phosphates
what is the dominant cation in the extracellular fluid?
sodium
what are the major anions in the extracellular fluid?
chloride
bicarbonate
what is the difference in composition between plasma and interstitial fluid?
plasma contains plasma proteins
t/f... osmolality is the same for intra and extracellular fluid
true
hypovolaemia involves depletion of...?
salt and water
what are the symptoms of hypovolaemia?
thirst
postural dizziness
weakness
what are the signs of hypovolaemia?
postural hypotension (>10mmHg drop in systolic)
tachycardia
dry mouth
reduced skin turgor
reduced eyeball tension
reduced urine output
reduced weight
confusion...>stupor...>coma
low JVP (not seen)
what is the single most accurate marker of body water?
body weight
which investigation results are expected in hypovolaemia?
increased Hb/Hcrt
increased plasma albumin
increased plasma urea
increased plasma renin
t/f... plasma sodium is a useful marker of hypovolaemia
false, concentration will usually not change but total body sodium will be low
what are the causes of hypovolaemia (sodium and water depletion)?
reduced Na/H2O intake
GIT losses of Na and H2O (e.g. vomiting, diarrhoea, NG tube suction, fistula)
renal losses (e.g. diuretics, sodium wasting conditions - aldosterone deficiency)
skin losses (e.g. excess sweating, burns)
internal sequestration (e.g. peritonitis, pancreatitis, crush injuries)
what are the sensors of a change in plasma volume?
volume receptors
pressure receptors
tubular [Na] receptors
what are the effector mechanisms following detection of a change in plasma volume?
neurohormonal (SNS, RAAS, vasopressin)
haemodynamic (fall in BP->reduced GFR)
what is the net result of effector mechanisms following a reduction of plasma volume?
increased renal Na/H2O reabsorption
what is the treatment for hypovolaemia?
IV normal (isotonic) saline (150mM NaCl/0.9g%)
what is the approximate baseline requirement for Na and water?
150 mmol Na
2-3 L water
what are the symptoms of hypervolaemia?
bilateral ankle swelling
breathless
what are the signs of hypervolaemia?
oedema
raised JVP
hepatomegaly
ascites
pulmonary oedema
pleural effusion
weight gain
t/f... hypertension is common in acute hypervolaemia
false, hypertension only occurs in chronic hypervolaemia
what tests are useful to detect hypervolaemia?
reduced Hb/Hcrt
reduced plasma albumin
CXR
t/f... plasma sodium increases in hypervolaemia
false, excess sodium is retained with water isotonically so conc will likely remain the same
what are the causes of hypervolaemia?
decreased renal function (reduced GFR)
oedema disorders (CCF, cirrhosis, nephrotic syndrome)
what is the treatment for hypervolaemia?
treat cause
salt and water restriction
diuretic treatment
what are the functions of the kidney?
regulatory - volume and composition of body fluids (includes excretion of wastes)
endocrine (erythropoietin, activated vit D, renin)
how many nephrons are in one kidney?
1 million
what structure brings blood toward the filtering unit of the kidney?
afferent arteriole
what structure does an efferent arteriole carry blood away from?
glomerulus (tuft of capillaries surrounded by tubular collecting system)
what is the single most important measure of kidney function?
GFR
t/f... glomerular filtrate contains cells and proteins>50D
false
how much plasma fluid is filtered by glomerulus into collecting tubule?
1/5
t/f... 99% of filtrate in collecting tubules is reabsorbed back into plasma?
true
t/f... some solutes and organic substances are secreted into collecting tubules
true
what does the efferent arteriole branch into?
peritubular capillaries
express renal blood flow (RBF) in terms of cardiac output
RBF=1/5 x CO
what is the renal plasma flow in terms of renal blood flow?
~0.5 of RBF
what is the GFR in terms of renal plasma flow?
1/5 x RPF
what is the average GFR?
100mL/min
what percentage of glomerular filtration is excreted as urine?
1%
what is the average urine flow?
1mL/min
what is anuria?
no urine is passed
what is oliguria?
<400mL/day
what is polyuria?
>3L/day
what is a normal urine output?
1.5L/day
what is the name for the very metabolically active part of the loop of Henle?
thick ascending limb (TAL)
t/f... the late distal tubule and the cortical collecting duct have the same function
true
where do collecting ducts form?
late distal tubule
where is sodium reabsorbed?
65% in proximal tubule
25% TAL
6% early distal tubule
2.5% cortical collecting duct
1% medullary collecting duct
how much filtered sodium is reabsorbed?
99.5%
how much filtered sodium is contained in final urine?
0.5%
what is the fractional excretion of Na?
0.5%
how does sodium move from filtered urine to cell in the proximal tubule?
paracellularly
sodium glucose cotransporter
NHE3
what does NHE3 do?
exchanges Na for H
what is the main mode of proximal tubule sodium reabsorption?
shunt (between cells)
t/f... sodium and water are reabsorbed isotonically in the proximal tubule
true
how is filtered sodium reabsorbed in the thick ascending limb?
NaK/2Cl cotransporter
t/f... no water crosses at the thick ascending limb of loop of Henle
true
where is sodium reabsorbed with a Cl?
early distal tubule
t/f... the early distal tubule is water permeable
false, it is water-impermeable
what is the approximate size of a kidney?
10 x 5 x 2.5cm
t/f... the kidneys are retroperitoneal, in the paravertebral gutters
true
which three muscles are related posteriorly to the kidneys?
psoas major
quadratus lumborum
aponeurosis of transversus abdominis
t/f... the left kidney is slightly lower than the right
false, the right kidney is lower than the left because of the liver
the anterior surfaces of the kidney face slightly...?
laterally
which nerves do the kidneys lie on?
subcostal
iliohypogastric
ilioinguinal
what surrounds the kidney?
fat and fascia
where is perinephric fat located?
between kidney and renal fascia
t/f... the anterior and posterior layers of the renal fascia are closely connected inferiorly
false
what structure gives rise to the ureter?
renal pelvis
what is the space deep to the renal hilum?
renal sinus
what is the most anterior structure of the renal hilum?
renal vein
t/f... the left renal vein is longer than the right renal vein
true
which two veins drain into the left renal vein?
left suprarenal vein
left gonadal vein
how does inflammation affect the renal capsule?
capsule will be more adherent to kidney
what does the renal vein travel between in the nutcracker space?
superior mesenteric artery and aorta
where do the right suprarenal and gonadal veins drain?
directly into IVC
what are the structures of the kidney that extend inward from the cortex between the pyramids?
renal columns
what is the collective term for the pyramids of the kidney?
medulla
what is contained in the renal sinus?
fat and collecting system
what is the name for the opening at the renal papilla?
minor calyx
what do the major calyces join to form?
renal pelvis
t/f... there are no anastomoses between segmental renal arteries
true
at what level do the renal arteries leave the abdominal aorta?
LV2
what is the lymphatic drainage of the kidney?
lateral aortic (lumbar) nodes
which four muscles are related posteriorly to the kidney?
diaphragm
psoas major
quadratus lumborum
transversus abdominis
which ribs are the kidneys related to?
right - R12
left - R11 & R12
what are the anterior relationships common to both kidneys?
suprarenal glands
small bowel
colon
what are the anterior relationships of the right kidney?
suprarenal gland
colon
jejunum/ileum
duodenum
liver
what are the anterior relationships of the left kidney?
suprarenal gland
colon
jejunum
stomach
spleen
pancreas
t/f... the gallbladder is related anteriorly to the right kidney
false, the gallbladder rests in front of duodenum and is not in contact with right kidney
where does the ureter start?
where the renal pelvis narrows
descibe the smooth muscle of the ureter
inner longitudinal
outer circular layer
how long is the ureter?
25 cm
what crosses the ureter anteriorly in the abdominal cavity?
gonadal vessels
what helps to prevent reflux of urine back into ureters
ureters pass obliquely through bladder wall
what is the blood supply to the ureter?
adjacent arteries which anastamose along ureter
in females, where do the ovarian vessels pass relative to the ureter?
anterior
where does the ureter pass relative to the ovary?
posterior
where does the ureter pass relative to the uterine artery?
inferior (water under bridge)
what is the "bridge" over the ureter in the male?
ductus deferens
what are the three sites of constriction along the ureter where a ureteric stone may lodge?
narrowing of renal pelvis transverse process L2)
pelvic rim (SI joint)
passage through wall of bladder (medial to ischial spine)
what type of pain is associated with ureteric stones?
ureteric colic
what is the result of obstruction of upper part of ureter?
hydronephrosis
what is the result of obstruction of lower part of ureter?
hydroureter and hydronephrosis
where does ureteric pain occur?
loin to groin
where does urinary bladder pain refer?
suprapubic
sacral
where do kidneys start their development?
pelvic cavity
why is a horseshoe kidney low?
can't pass up beyond SMA
t/f... the empty bladder in an adult is entirely within pelvic cavity
true
t/f... an empty bladder in a neonate lies entirely in pelvic cavity
false, it is abdominal in children until after puberty
what is the lowest point of the bladder?
neck
descibe the inner surface of the bladder
rugae
trigone (triangular area situated posteriorly)
what is the most anterior structure in the pelvis in both sexes?
bladder
what are the superior relationships of the bladder in males and females?
male - coils of intestines
female - coils of intestines and uterus
what is posterior to bladder in a female?
cervix and upper part of vagina
what are the lateral relations of the bladder?
levator ani
obturator internus
what lies anterior to bladder in both males and females?
retropubic space and puic symphysis
what is directly behind bladder in males?
rectum
ductus deferens
seminal vesicles
what lies below the bladder in males?
prostate
what is the urachus?
fibrous remnant of allantois that connects bladder to umbilicus
how long is the female urethra?
4cm
what are the boundaries of the female urethra?
internal urethral orifice and external urethral orifice
which sphincter of the urethra is under voluntary control?
external urethral sphincter
where does the urethra open in a female?
between labia minora (vestibule)
where is the sphincter vesicae?
bladder neck
what are the parts of the urethra in the male?
preprostatic urethra
prostatic urethra
membranous urethra
spongy urethra
where is the narrowest part of the urethra in a male?
tip of glans penis
where is the least dilatable part of the male urethra?
external urethral sphincter
where is the most dilatable part of the male urethra?
prostatic part
what is the normal plasma osmolality?
290 mmol/kg
what is the normal range for plasma osmolality?
285-295
what is the possible range for urine osmolality?
50-1200
will a concentrated urine have high or low osmolality?
high
where are the glomeruli located?
cortex
where does the loop of Henle extend?
into the medulla
t/f... the loop of Henle generates a gradient of tissue osmolality in medulla
true
what is required for passive water reabsorption from the collecting duct?
ADH
what triggers the presence of ADH at the collecting duct?
increased plasma osmolality
t/f... collecting duct can allow passive water reabsorption when ADH is present
true
what change in plasma osmolality triggers ADH?
1-2%
t/f... the descending limb of the loop of Henle is water permeable and has no active solute transport
true
t/f... the ascending limb is water tight and has active solute transport
true
where in the nephron does fluid have a lower osmolality than plasma?
fluid entering and in the early distal tubule
when will the minimum urine osmolality occur?
no ADH present
sodium continues to be reabsorbed
when will maximum urine osmolality occur?
ADH present
what allows water to be reabsorbed from the collecting duct?
ADH
which solute amplifies the urine concentrating process?
urea
where is urea trapped when ADH is present?
medulla
what is the name for the capillaries supplying loop of Henle and medulla?
vasa recta
which factors would increase concentrating power of kidney?
increased length of loop
increased pump capacity of TAL
decreased urine flow rate
what is required to concentrate urine?
adequate GFR
loop action
ADH
what is required to dilute urine?
adequate GFR
loop action
early distal tubule action
no or zero ADH
what detects changes in plasma osmoreceptors?
osmoreceptors
what is stimulated by osmoreceptors?
thirst
synthesis of ADH
what is ADH?
peptide of 9 amino acids
what is osmotic regulation of ADH release?
as osmolality increases, ADH conc increases rapidly
what factors contribute to non-osmotic regulation of ADH?
hypovolaemia
hypotension/shock
pain, nausea, stress
what percentage change is required for non-osmotic regulation?
10%
what are the two actions of ADH?
H2O reabsorption
vasoconstriction
where does ADH act?
at V2 receptors at:
cortical collecting duct
medulla collecting duct
what type of receptor is V2?
G protein coupled
what is the action of protein kinases activated by ADH?
cause AQP2 channels to move to apical membrane
what are the features of diabetes insipidus?
increased plasma osmolality
increased plasma sodium
what is a diuretic?
an agent that increases the urine flow rate
what percentage of filtered sodium is excreted?
0.5%
what is the average fractional excretion of H2O?
1%
t/f... the major mechanism of diuresis is to increase GFR
false
what are the xanthines?
adenosine receptor blockers
what is the effect of adenosine in the afferent arteriole?
vasoconstriction
how do xanthines increase the GFR?
block adenosine receptors->vasodilation in afferent arteriole->increase GFR
which drugs achieve their diuretic effect by increasing GFR?
xanthines
digoxin
how does digoxin increase GFR?
increase in CO
what is the major mechanism of diuresis?
decreased tubular reabsorption of sodium
how does an osmotic diuretic work?
decreases tubular reabsorption of a non-reabsorbable solute
at what plasma level is glucose non-reabsorbable?
>10 mmol/L
what substance if given IV is filtered but nor reabsorbed?
mannitol
when is mannitol given?
cerebral oedema
what is the major form of diuretic drug?
natriuretics
which transporter contributes to sodium reabsorption in the proximal tubule?
GLUT2
the amount of hydrogen secreted in the proximal tubule is equal to the amount of ... in the lumen?
bicarbonate
which exchanger contributes to sodium reabsorption in the proximal tubule?
Na/H exhanger
what makes carbonic acid (H2CO3)?
CO2 and H2O
what does carbonic acid dissociate into?
HCO3 and H
what is required for CO2 and H2O to produce carbonic acid?
carbonic anhydrase
what is lost in the urine with acetazolamide?
Na and HCO3
what condition may be treated with acetazolamide?
glaucoma
which transporter on the apical membrane contributes to sodium reabsorption in the thick ascending limb?
Na2ClK cotransporter
what causes the positive ions to move through gap junctions between TAL cells?
positive charge in lumen
what does frusemide inhibit?
Na2ClK carrier
what is the effect of frusemide on electrolyte excretion?
loss of sodium, chloride, potassium, calcium, magnesium
what is the net effect of frusemide?
hypokalaemia
alkalosis
where is acid lost with frusemide treatment?
cortical collecting duct
how much water is reabsorbed in the TAL?
zero
what transporter is involved in sodium reabsorption in the early distal tubule?
NaCl cotransporter
which diuretics act at the early distal tubule?
thiazides
which diuretics are the most powerful?
loop diuretics (25% of sodium reabsorption occurs in the TAL cf 6% in early distal tubule)
which electrolytes are lost with thiazide administration?
Na, Cl, Mg, K
why is K lost in the urine with thiazides?
lumenal Na is swapped with K and H at the cortical collecting duct
at what point is water retained in the lumen with loop diuretics and thiazides?
CCD (water is trapped by cations in the lumen)
what are the complications of thiazides?
hyponatraemia
hypovolaemia
hypokalaemia
alkalosis
t/f... thiazides increase calcium excretion
false, thiazides result in reduced calcium excretion
how does calcium enter and exit the early distal tubule cells?
calcium channel in apical membrane
ca/3na exchanger in basolateral membrane
what cells are present in the late distal tubule and cortical collecting duct?
principal (2/3 of cells)
intercalated (smaller, 1/3 of cells)
t/f... sodium enters the principal cell down its electrochemical gradient through a channel
true
t/f... sodium enters the principal cell down its electrochemical gradient through a carrier
false
which channel does Na enter the principal cell through?
epithelial sodium channel
which direction and through which channel does potassium move from the principal cell in the ED/CCD?
into the lumen through RoMK
what drives K secretion in the early distal tubule and the cortical collecting duct?
electro and chemical gradients
how is acid secreted from the intercalated cells?
hydrogen ATP ase
why is chloride absorbed between the cells in the LD/CCD?
lumen has a negative charge which drives chloride across
how is the huge sodium influx in the LD/CCD counteracted?
K secretion (principal cell)
H secretion (intercalated cell)
Cl absorption (between cells)
what stimulates the processes involved in sodium reabsorption in the LD/CCD?
aldosterone (upon binding to a cytoplasmic receptor)
what does amiloride do?
inhibits the epithelial Na channel
what losses occur with amiloride?
Na
Cl
H2O
what is retained with amiloride?
K and H
what is spiranolactone?
aldosterone antagonist (and a K-sparing diuretic)
which diuretic can be given to a patient allergic to sulphonamides?
ethacrynic acid (acts at TAL)
which diuretics are sulphonamides?
ACTZ
frusemide
thiazides
which diuretic is a pyrazine?
amiloride
which diuretic is a steroid?
spironolactone
what are the indications for diuretic therapy?
hypervolaemic states: oedema (CCF, cirrhosis, nephrotic syndrome)
hypertension
other: increased blood calcium (frusemide), renal ca stones (thiazide)
etc
which diuretic is indicated in the oedematous conditions CCF, cirrhosis and the nephrotic syndrome?
thiazide or frusemide
why are diuretics relatively ineffective in chronic kidney disease?
these patients have a greatly reduced GFR and diuretics act on lumenal carriers
which diuretic is used to treat mild hypertension?
thiazide alone
which diuretic is indicated in severe hypertension?
thiazide in combination
what are the three categories of adverse drug reactions of diuretics?
physiological
metabolic
miscellaneous
what are the physiological complications of diuretics acting at the TAL and the early distal tubule?
hypovolaemia
hyponatraemia
hypokalaemia
hypomagnesaemia
metabolic alkalosis
what are the physiological complications of diuretics acting at the late distal tubule/cortical collecting duct?
hypovolaemia
hyponatraemia
hyperkalaemia
acidosis
what are the metabolic complications of diuretic therapy?
increased glucose
increased lipids
increased uric acid
which diuretics are associated with metabolic complications?
frusemide
thiazides
what are the miscellaneous complications of thiazides?
allergies
GIT disorders (cholecystitis, pancreatitis)
erectile dysfunction
which arteries perfuse the renal cortex?
arcuate arteries
t/f... the distal tubule abuts onto the glomerulus
true
what regulates sodium reabsorption?
volume
what regulates water reabsorption?
osmolality
t/f... osmolality regulation overrides volume regulation
false
give the formula for clearance
clearance=([U]xvolume)/[P]
when does clearance roughly equate to GFR?
if a substance is freely filtered at the glomerulus and neither reabsorbed or secreted
clearance of which substance equates to GFR?
creatinine
what happens to the afferent arteriole when the blood pressure is low?
afferent arteriole constricts
what happens to the afferent and efferent arterioles when blood pressure is high?
afferent arteriole dilates
efferent arteriole constricts
what is the effect of angiotensin II?
vasoconstriction
which factors will increase the tubular reabsorption of sodium?
increased sympathetics tone
angiotensin II
aldosterone
which factors reduce the tubular reabsorption of Na?
increased ANF->increased dopamine
increased renal perfusion pressure->increased interstitial hydrostatic pressure
renal prostaglandins
what stimulates the Na-H countertransporter in the proximal tubule?
angiotensin II
where does ANP inhibit sodium reabsorption?
medullary collecting duct
where does aldosterone act to stimulate reabsorption of sodium?
distal tubule
what are the ECG changes of hypokalaemia?
T wave flattening
depression of ST segment
prominent U waves
what are the signs of dehydration?
reduced skin turgor
reduced eyeball tension
loss of light reflex of tongue
dry mouth
what are the signs of overhydration?
raised JVP
tachypnoea
visible apex beat
ascites
peripheral oedema
what are the signs of hyperkalaemia?
weakness
cardiac changes
what are the signs of uraemia?
anaemia
leukonychia
depression of CNS
peripheral neuropathy
scratch marks
foetor
asterixis, hiccups
purpura
calcium deposits
what conditions may result in enlarged kidneys?
polycystic kidney disease
obstruction/stones
what sign may indicate renal artery stenosis?
renal bruit
how is the bladder examined?
palpation and percussion
where in the nephron is urine maximally concentrated?
tip of loop of Henle
in what situation is the collecting duct impermeable to water?
absence of ADH
how does ADH affect the collecting duct?
makes it water-permeable
what is ADH released in response to?
high plasma osmolality or low circulating plasma volume
what is the most common cause of oliguria?
volume depletion
what are the signs of volume depletion?
tachycardia
postural hypotension
reduced skin turgor
reduction in weight
what are the lab test results that support a diagnosis of volume depletion?
urea to creatinine ratio > 80
elevated Hcrt
urinary osmolality > 450
urine sodium conc <20
how is fractional excretion of sodium calculated?
U:P sodium/U:P creatinine
what does a fractional excretion of Na less than 1% indicate?
volume depletion or other pre-renal factors
what does a fractional excretion of sodium of greater than 1% indicate?
acute tubular necrosis
what is renal clearance?
volume of plasma from which a substance has been removed and excreted in the urine per unit time
what is the formula for renal clearance?
C[x] = U[x] x V / P[x]
give an example of a substance whose clearance is equal to the RPF?
para-aminohippuric acid
what is the clearance of plasma glucose within the normal range?
zero
why does glucose appear in the urine of diabetic patients?
the filtered load exceeds the tubular transport maximum
what performs protein degradation in the lumen of the GIT or in cells?
proteases
how do proteases degrade protein?
hydrolyse peptide bonds
when is protein degradation accelerated?
starvation
chronic disease
in starvation and chronic disease, how are amino acid pools replenished?
protein breakdown by extracellular chemical species like TNF (cachexin)
what is the first step of amino acid deamination?
amino-transferase (transaminase) reaction
what are the products of a transaminase reaction?
keto-acid and glutamate
what is deaminated in step 2 of amino acid deamination?
glutamate
which coenzyme is required by aminotransferases?
pyridoxal phosphate
what is the major site of aminotransferase synthesis and amino acid deamination?
liver
what is produced when glutamate is deaminated?
alpha-ketoglutarate and ammonium ions
which ion contributes to hepatic encephalopathy?
NH4+
how are NH4+ ions eliminated?
urea cycle
how is urea excreted?
glomerular filtration in the kidney
where is urea synthesised?
liver
where is urea excreted?
kidney
t/f... patients with acute and chronic renal failure will have elevated serum urea
true
which amino acid donates an amino group in urea synthesis?
aspartate
t/f... ATP is required for urea synthesis
true
when does massive elevation of blood urea levels occur?
end-stage renal failure
what is the major extracellular buffer of H+?
HCO3-
what are the intracellular buffers of H+?
HCO3- and proteins
t/f... most buffering in respiratory conditions is extracellular
false, plasma CO2 is the acid of respiratory acidosis so the plasma HCO3-/CO2 cannot act as a buffer
where does compensation against metabolic acid-base disturbances occur?
lungs
where does compensation against respiratory acid-base disturbances occur?
kidney
what happens in response to metabolic acidosis?
medullary chemoreceptor stimulates ventilation so that blood PCO2 falls by 1 to 1.5 times the fall in HCO3
what happens in response to metabolic alkalosis?
ventilation is depressed to retain acid (PCO2 does not rise above 55 because hypoxic drive to respiration takes over)
t/f... in acute respiratory acidosis, the plasma HCO3- will be greater than 30
false, this occurs in chronic respiratory acidosis when there has been sufficient time for ammoniagenesis
what does plasma HCO3- fall to in respiratory alkalosis?
15-18 mmol/L
what is the renal response to acidosis?
increased ammoniagenesis
t/f... renal correction of acidosis by ammoniagenesis occurs immediately
false, enzymes must be induced so there is a lag phase (12-24 hours) and peak NH4+ excretion may not occur for up to 5 days with continuing acidosis
t/f... renal correction of metabolic alkalosis occurs rapidly
true
what may prevent the kidneys from correcting a metabolic acidosis?
concomitant dehydration
what is the mechanism of renal correction of metabolic acidosis?
dumping of HCO3-
what is normally the first abnormality to occur in renal failure?
ability of kidney to concentrate urine and retain water
how much filtered sodium is reabsorbed?
99%
what type of sodium imbalance usually occurs with renal failure?
salt and water retention
what adaptive mechanisms occur in response to hyperkalaemia?
increased aldosterone and Na/K ATPase activity
what is the major site for nonvolatile acid excretion?
kidney
how much nonvolatile acid requires excretion every day?
approx 1meq/kg of body weight
what are the consequences of failure to excrete phosphate?
acid-base disturbances
disorders of calcium metabolism
what are the two mechanisms of acute tubular necrosis?
ischaemic
nephrotoxic
which type of ATN is associated with prominent tubular epithelial cell necrosis?
toxic
what is the major factor in ischaemic ATN?
shock (systemic hypotension)
what occurs in ischaemic ATN?
significant reduction in renal blood flow -> reduced perfusion of cortex compared to medulla -> oliguria or anuria
t/f... urine formed in the oliguric phase of ischaemic ATN is isotonic with plasma
true
what are the histological changes seen in ischaemic ATN?
loss of brush border and flattening of epithelial cells in proximal tubules
dilation of prox and distal tubules
finely granular brown casts
necrosis and desquamation of individual epithelial cells
destruction of tubular basement membranes
mitotic activity
mild interstitial oedema
light chronic inflammatory cell infiltrate
what are the possible mechanisms for the oliguria/anuria of ischaemic ATN?
tubular back-leak
tubular obstruction by casts
arteriolar vasoconstriction
where is cell damage most obvious with nephrotoxic ATN?
proximal tubules
what is rhabdomyolosis?
breakdown of large masses of striated muscles with the resultant leakage of myoglobin and other intracellular constituents into the bloodstream
what are the most common causes of rhabdomyolosis?
crush injuries
trauma
exertion
alcohol
drugs
what are the symptoms of rhabdomyolosis?
may be asymptomatic
muscle pain
stiffness
weakness
what are the signs of rhabdomyolosis?
tender, swollen muscles with a doughy feel
black or burgundy-coloured urine
what are the biochemical abnormalities of rhabdomyolosis?
marked elevations of creatinine kinase and other muscle enzymes
hyperkalaemia
hyperphosphataemia
hyperuricaemia
hypocalcaemia
low urea:creatinine ratio
what is the pathology of rhabdomyolosis associated acute renal failure?
acute tubular necrosis with pigmented casts in distal tubules
how is established rhabdomyolosis managed?
correction of volume deficit with normal saline
alkaline diuresis maintained with saline, mannitol and bicarb
dialysis once ARF is established
why does hyperkalaemia need early treatment in rhabdomyolosis?
the associated hypocalcaemia enhances the cardiotoxicity
what are the major complications associated with haemodialysis?
vascular access difficulties
cardiac disease
bone disease
B2 microglobulin deposition
malnutrition
what are the major complications associated with peritoneal dialysis?
peritonitis
exit site infections
cardiac disease
malnutrition
difficulties with adequate dialysis once residual renal function disappears
how is digoxin excreted by the kidney?
filtered at the glomerulus
list some drugs that are excreted by the kidney via secretion by the proximal tubule
probenecid
penicillin
thiazides
frusemide
salicylates
what is the effect of renal impairment on steady state blood levels of drug?
it will take longer for steady state levels to be achieved
t/f... renal impairment prolongs the half life of a drug
true
t/f... renal impairment shortens the half life of a drug
false
which drugs cause pre-renal ARF?
ACE inhibitors
angiotensin II receptor blockers
NSAIDs
radiocontrast agents
what dilates the afferent arteriole?
prostaglandins
what constricts the efferent arteriole?
angiotensin II
how do ACE inhibitors and ARBs affect the efferent arteriole?
prevent vasoconstriction
how do NSAIDs affect the afferent arteriole?
prevent dilation (block formation of prostaglandins)
why do non-steroidals increase blood pressure?
prostaglandins promote sodium loss in the loop of Henle
which drugs may cause ATN?
aminoglycosides
cisplatinum
amphotericon
which drugs may cause acute interstitial nephritis?
antibiotics
NSAIDs
PPIs
which drugs may cause post renal obstruction?
analgesics
methysergide
HIV therapies
which drugs may cause chronic kidney disease?
analgesics
lithium
which drugs may cause the nephrotic syndrome?
NSAIDs
penicillamine
gold
captopril
which receptor do ARBs target?
AT1a receptor
how do ACE inhibitors and ARBs lower BP?
reduce vasoconstriction and Na reabsorption
what are the causes of prerenal ARF?
intravascular volume depletion
decreased cardiac output
systemic vasodilation
renal vasodilation
drugs
what are the causes of post-renal ARF?
ureteral obstruction (bilateral)
bladder obstruction
urethral obstruction
what are the causes of intrinsic ARF?
ischaemic ATN
nephrotoxic ATN
acute interstitial nephritis
acute glomerulonephritis
intratubular obstruction
what might a low urinary sodium and concentrated urine indicate?
pre-renal ARF
what occupies the space between podocytes?
filtration slit and slit diaphragm
what is the main protein composing the slit diaphragm?
nephrin
what does the intracellular domain of nephrin interact with?
cytoskeletal proteins in the podocytes (podocin, NEPH1, ZO-1)
what does the extracellular domain of nephrin interact with?
extracellular domain of nephrin from neighbouring podocyte
what enables podocytes to contract?
F-actin (linked to ZO-1)
what does the ZO-1 link to in the podocyte?
F-actins
integrins (expressed by podocytes linking them to basement membrane)
what secretes the proteins in the basement membrane?
podocytes
t/f... the podocyte membrane is negatively charged
true
what determines filtration of a substance?
molecular size
charge
what size of a neutral substance is freely filtered?
<10kDa
what size of a neutral substance is the upper limit of filtration?
70kDa
which are more easily filtered, anions or cations?
cations
t/f... water is freely filtered at the glomerulus
true
name three solutes that are freely filtered
water
glucose
inulin
how much myoglobin is filtered?
75%
why is very little albumin filtered?
albumin is negatively charged
what stimulates contraction of glomerular mesangial cells
ATII
ADH
growth factors
endothelin
what stimulates relaxation of glomerular mesangial cells?
ANP
NO
PGE2
what is the effect of relaxation of mesangial cells?
increase surface area of capillaries for filtration and therefore increase filtration rate
what is the effect of contraction of mesangial cells?
decrease filtration rate
what are the functions of the glomerular mesangial cells?
contractile
secrete mesangial matrix
behave like macrophages
proliferation
what factors determine GFR?
surface area for filtration
filtration membrane permeability
net filtration pressure
what pressures contribute to glomerular filtration pressures?
hydrostatic pressure in capillary (main pressure) (=55)
hydrostatic pressure in Bowman's capsule (=10)
colloid osmotic pressure in capillary (=25)
colloid osmotic pressure in Bowman's capsule (=0)
t/f... the net filtration pressure decreases along the length of glomerular capillary
true
t/f... GFR is very tightly regulated at 125 ml/min
true
over what range of MAP will the GFR remain constant?
90-200 mm Hg
what happens to the afferent arteriole when the smooth muscle is stretched?
stretch releases intracellular calcium which causes the muscle to contract
what is the effect of an increased afferent BP on blood flow to the glomerulus?
blood flow is reduced due to vasoconstriction of the arteriole
what is the effect of adenosine on the afferent arteriole?
vasoconstriction
how does the tubuloglomerular feedback mechanism respond to increased chloride conentrations?
macula densa cells sense high chloride concentrations and respond by releasing adenosine which constricts the afferent arteriole, reducing the flow rate
how does the tubule sense changes in flow?
changes in chloride concentration
what is the response by macula densa cells to a reduced flow rate in the tubules?
secretion of PGE2 which causes vasodilation of the afferent arteriole and renin secretion from granular cells of juxtaglomerular apparatus
renin secretion leads to production of ATII which constricts efferent arteriole
secretion of NO causing vasodilation of afferent arteriole
what is Bartter's syndrome?
NKCC2 mutation (increased renin, vasodilation of afferent arteriole)
t/f... renal sympathetic nerve activity is low under normal circumstances
true
what are the effects of renal sympathetic nerve activity on the afferent arteriole?
vasoconstriction (via noradrenaline)
[it also increases renin secretion]
what is the general feature of the nephrotic syndrome?
massive proteinuria
t/f... podocytes can undergo regenerative proliferation
false
t/f... ACE inhibitors can improve nephrin expression
true
how are volatile acids excreted?
by the lungs
what excretes nonvolatile acids?
kidney
what is the net acid secretion for a 70 kg person?
70 meq/day
what is the major acid excreted?
ammonium ions
t/f... under normal circumstances, the kidney dumps bicarbonate
false
give the equation for net acid excretion
net acid excretion = NH4+ + TA(H2PO4-) - HCO3-

[70 = 40 + 30 - 0)
what is the main system of buffering both intracellularly and extracellularly?
bicarbonate
what are the systems of non-bicarbonate buffering?
protein
phosphate
bone
where is bicarbonate reabsorbed?
proximal tubule
what is the main titratable acid?
HPO42-
where is HPO42- acidified?
late distal/CCD
where is NH3 produced?
proximal tubule
where is NH3 acidified?
late distal/CCD
what is the net result of bicarbonate reclamation?
sodium and bicarbonate reabsorption
how is bicarbonate generated by the proximal tubule?
titratable acids and NH4+ are formed by the H from the Na/H exchanger and a new bicarb is absorbed via the Na/HCO3- transporter
where is NH3 made?
proximal tubule cell
where are hydrogen ions added to NH3?
tubular lumen
what is generated via the process of acidification of TA and NH3?
a new bicarbonate
how does the kidney deal with acidosis?
makes more ammonia (delay phase for induction of enzymes)
what are the immediate, compensatory and correction phases to metabolic acidosis?
buffering (intracellularly and extracellularly)
compensation via ventilation
renal correction
what are the three phases of defence against acid-base disorders?
buffering
compensation
correction
what is the range for pCO2?
35-45
what is the range for pH?
7.35 - 7.45
what is the range for HCO3-?
24-28
what is the normal range for pO2?
80 - 100
how much acid is immediately buffered in metabolic acidosis?
50% of acid load
what is required for compensation of metabolic acidosis?
ventilation
tissue perfusion
give the A-a gradient equation?
A-a gradient = FiO2 - pO2 - pCO2x1.2
what should the A-a gradient be below?
15
what may cause an inadequate renal correction of metabolic acidosis?
renal failure
renal tubular acidosis
what is the equation for the plasma anion gap?
Na + K - Cl - HCO3
what should the plasma anion gap be?
15 +/- 4
what may a normal plasma anion gap in metabolic acidosis indicate?
bicarbonate loss from bowel or kidney
what may a raised plasma anion gap indicate?
increased load of acid (endogenous or exogenous)
reduced excretion (renal failure)
what should the osmolar gap be below?
15
what does a metabolic acidosis and a raised osmolar gap indicate?
toxic alcohol
what is the normal threshold for HCO3 reabsorption?
25
how does proximal RTA affect the HCO3 threshold?
RTA lowers the threshold so there is bicarbonate wasting
where is the defect in type 1 RTA?
H ATPase
what electrolyte imbalance is associated with type 1 RTA?
hypokalaemia
where is the defect in type 4 RTA?
ENaC in the principal cell
what electrolyte imbalance is associated with type 4 RTA?
hyperkalaemia
which type of RTA is associated with disturbed calcium metabolism?
type 1
how much of the load is buffered in metabolic alkalosis?
30%
t/f... the renal correction of metabolic alkalosis occurs slowly
false, it is rapid
why does the pCO2 remain less than 55 in compensation of metabolic alkalosis?
hypoxic drive to breathe takes over
what are the two phases of metabolic alkalosis?
generation
maintenance
what are the main GI and renal causes of metabolic alkalosis?
vomiting
diuretic therapy
what is the treatment of metabolic alkalosis?
give volume (rather than acid)
which toxins build up in the failing kidney?
urea
potassium
phosphate
acid
what are the features of toxin build up in the failing kidney?
urea (nausea)
potassium (weakness and hearth rhythm)
phosphate (itch, PTH and bone disease)
acid (breathlessness and bone disease)
what are the features of water retention?
fluid in the lungs (breathlessness)
fluid in the legs (oedema)
high blood pressure
what blocks tubular secretion of creatinine?
cimetidine
t/f... urea clearance overestimates the inulin GFR
false, it underestimates the GFR because there is some tubular reabsorption of urea
in what situations is a urine collection inaccurate?
over acute change (ARF or during recovery)
t/f... bicarbonate is freely filtered by the glomerulus
true
where is bicarbonate reabsorbed?
majority in proximal tubules
some in distal tubule
where is the defect in type 2 renal tubule acidosis?
bicarbonate reabsorption in proximal tubule
what is the normal range for plasma potassium?
3.5 - 5
what effect do insulin, catecholamines and increased pH have on potassium?
push potassium into cells
how is potassium excreted by the body?
90% - urine
10% - gut
how much potassium is reabsorbed in the proximal tubule?
65%
how much potassium is reabsorbed in the TAL?
25%
how much potassium is reabsorbed in the early distal tubule?
zero
how much potassium is secreted in the early distal tubule?
zero
where in the nephron is potassium secreted?
late distal tubule
how much potassium can be secreted in the nephron?
0 - 20% (variable)
what is the lowest amount of potassium to be excreted?
5% of filtered load
how much filtered potassium is excreted in the urine?
5 (on a low K diet) - 30 (on a high K diet)%
what regulates potassium secretion in the late distal/CCD?
lumen factors: Na delivery, flow rate, negative potential difference
blood factors: aldosterone, plasma K, increased pH
how does increased dietary potassium stimulate potassium secretion?
increase aldosterone
increase plasma K
t/f... increased plasma K directly stimulates the zona glomerulosa to release aldosterone
true
what directly stimulates the adrenal gland to release aldosterone?
increased plasma K
angiotensin II
what stimulates renin secretion?
decreased ECFV
decreased BP
what are the effects of aldosterone on the kidney?
decrease Na excretion
increase K secretion
what are the effects of hypokalaemia?
skeletal muscle weakness
cardiac effects (ECG changes, ectopics)
ileus (pseudoobstruction)
polyuria (nephrogenic DI)
renal fibrosis
what are the ECG changes of hypokalaemia?
T wave flattened
U waves
t/f... acute hypokalaemia is associated with polyuria and renal fibrosis
false, these changes occur with chronic hypokalaemia
what can cause redistribution of potassium into the cells?
insulin
adrenaline
increased ECF pH
what are the causes of hypokalaemia?
excess potassium losses (urine or GIT)
reduced intake
redistribution
what does hypertension associated with low blood potassium indicate?
tumour producing too much aldosterone
what are the causes of potassium losses in the urine?
diuretics
excess aldosterone
others
what are the causes of potassium losses in the GIT?
vomiting
diarrhoea
what is the treatment of hypokalaemia?
reverse cause
replace KCl (oral or IV)
amiloride
what are the effects of hyperkalaemia?
skeletal muscle weakness
ECG changes (T wave tenting, broadening of QRS, sine wave looking)
what are the causes of hyperkalaemia?
in vitro haemolysis
redistribution
increased intake
renal retention of K
what factors may cause potassium to move out of cells?
reduced insulin
beta blockers
acidosis
how is hyperkalaemia treated?
stabilise excitable tissue (give calcium infusion)
shift potassium into cells (insulin + glucose, beta2 agonist, NaHCO3)
remove K (diuretic, resonium, dialysis)
which has the lower mortality, transplant or dialysis?
transplant
t/f... high deceased donor rates push down living donor rates
true
what is the mortality for living kidney donors?
1 in 3000
which formula estimates GFR using P(cr), age and sex?
MDRD formula
which formula estimates GFR using P(cr), age, weight and sex?
Cockroft-Gault
why does diuretic therapy cause hypokalaemia and high bicarbonate?
due to LD/CCD loss of K and H
t/f... the early distal tubule is a diluting segment
true
t/f... loop diuretics reduce both the concentrating and diluting capacity of the nephron
true
t/f... thiazide diuretics reduce both the concentrating and diluting capacity of the nephron
false, thiazides reduce the diluting capacity only
why does hyponatraemia occur with diuretic therapy?
plasma is diluted when water loaded because the urine diluting capacity of the nephron is impaired by the diuretic
what effect does hypokalaemia have on the membrane potential difference?
increases pd -> increases excitability (ectopics, ventricular arrhythmias)
how does an increased pd lead to ectopics and arrhythmias?
not completely understood, thought to be an increase in Na channel activity
how does high K result in asystole?
reduces potential difference -> (reduces Na channel activity) -> reduces excitability (slows APs -> conduction ceases)
what are the three main stimuli for renin release?
drop in perfusion pressure in afferent arteriole (hypotension, hypovolaemia)
sympathetic stimulation
low [Na] in early distal tubule (detected by macula densa cells)
what is the main site of angiotensin II production?
lungs
what are the actions of angiotensin II?
acts on adrenal gland to release aldosterone
acts on proximal tubule to increase Na reabsorption
constricts arterioles
what do AII and ADH retain?
AII - Na
ADH - water
what is the main dilator of afferent arteriole?
prostaglandins
t/f... AII in high concentrations acts to constrict the efferent arteriole
false, this happens with low concentrations of AII
what is the effect of high concentrations of AII?
afferent arteriole vasoconstriction
mesangial contraction
(net effect: reduction of GFR)
what acts to constrict the afferent arteriole?
high conc of AII
Noradrenaline
how much bicarbonate is reabsorbed in the proximal tubule?
100%
what are the two buffer systems (and their limits) in the nephron?
filtered HPO4(2-) (limited to 30 mmol H+/day)
NH3
what causes a normal anion gap metabolic acidosis?
loss of HCO3 (prox tubule or gut)
what causes a high anion gap metabolic acidosis?
gain of new H+ e.g. ketoacidosis or lactic acidosis
what contributes to the anionic charge barrier of the endothelial layer of the glomerular capillaries?
heparan sulphate
what are the three layers of the glomerular basement membrane?
lamina rara externa
lamina densa
lamina rara interna
what prevents albumin from being filtered at the glomerulus?
physical barrier (GBM)
charge barrier
what type of collagen forms the GBM?
collagen type IV in a mesh arrangement
what controls the filtration of protein?
pressure
renal plasma flow
protein concentration
size barrier
charge barrier
what are the causes of proteinuria (mechanisms)?
increased load
increased capillary wall permeability
impaired tubular reabsorption
what type of casts appear in overload proteinuria?
granular casts (fractured when cut)
what is the most common cause of proteinuria?
glomerular injury
what are the common presentations of proteinuria?
asymptomatic
frothy urine
nephrotic syndrome
what are the consequences of filtration of plasma proteins?
loss of trace elements, hormones, vitamins
Ig loss (infection)
coagulation factor losses (thromboembolism)
what are the consequences of albuminuria?
tubular dysfunction following reabsorption
hypoalbuminaemia (increased hepatic lipoprotein synthesis -> hyperlipidaemia -> lipiduria)
oedema
what is the clinical effect of loss of vitamin D in the urine?
hypocalcaemia
what is the nephrotic sydnrome?
proteinuria (>3.0 gm/day)
hypoalbuminaemia
oedema
what is the mechanism of hypoalbuminaemia in the nephrotic syndrome?
urinary losses of albumin
failed hepatic synthesis
what is the commonest cause of adult nephrotic syndrome?
membranous GN
what are the pathological features of membranous GN?
thickened GBM (subepithelial deposits, "spikes", "tram tracks")
what are the causes of membranous GN?
idiopathic
secondary (neoplasia, SLE, RA, penicillamine, gold therapy, Hep B, Hep C, syphilis, sarcoid, schistosmiasis)
who has a high risk of ESRD with membranous GN?
nephrotic syndrome
male
high serum creatinine
poor response to therapy
how is membranous GN treated (non-nephrotic and nephrotic)?
non-nephrotic: diuretics and wait 6 months
nephrotic: steroids, cyclophosphamide/chlorambucil, ACEI/ARB and statins
what are the clinical features of focal and segmental glomerulosclerosis?
nephrotic or subacute proteinuria
reduced GFR
hypertension
mild haematuria
what percentage of patients with focal and segmental glomerulosclerosis will have ESRD at 5 years?
10-50%
how is FSGS treated?
ACEI
what is the pathophysiology of primary FSGS?
toxin to visceral epithelial cells
what is the most common cause of nephrotic syndrome in children?
minimal change disease
what are the features of minimal change disease?
selective proteinuria/nephrotic sydnrome
benign urine sediment, normal serum creatinine
how is minimal change disease treated?
empirical prednisolone
cyclophosphamide/Cyclosporin A for relapse
what is the pathophysiology of MCD?
T cell lymphokines released and cause loss of anionic charge barrier and podocyte injury
what is seen on EM with MCD?
foot process fusion, no deposits
what is seen on LM and IF with MCD?
minimal change
what are the three conditions of proteinuria?
transient
orthostatic
persistent
how is proteinuria treated?
treat underlying condition
salt restriction
adequate (not excessive) protein intake
diuretics
ACEI
control HTN
warfarin if thromboembolism
pneumovax
what type of proteinuria indicates glomerular disease?
albuminuria
what occurs in response to volume depletion?
volume receptors (in carotid sinus and aortic arch) increase sympathetic activity
vasoconstriction
renal salt and water retention
ADH secretion
renin secretion and AII production (vasoconstriction)
what occurs in response to overhydration?
right atrial stretch receptors release ANP which mediates an acute, corrective natriuresis
how is the nephritic syndrome characterised?
active urine sediment with haematuria, proteinuria, fluid retention and consequent hypertension and oedema formation
how is the nephrotic syndrome characterised?
oedema, hypoalbuminaemia and heavy proteinuria (>3.5g/day)
what are the usual causes of the nephrotic syndrome?
glomerulonephritis
diabetic nephropathy
vasculitis
renal amyloidosis
why does hypoalbuminaemia occur in the nephrotic syndrome?
excessive renal protein losses
increased renal protein catabolism
blunted hepatic albumin synthesis
what is the mechanism of oedema in the nephrotic syndrome?
reduction of plasma colloid osmotic pressure due to hypoalbuminaemia
renal salt and fluid retention
t/f... blood volume is usually decreased in the nephrotic syndrome
false, blood volume is often normal
how is oedema in CCF caused?
renal salt and water retention secondary to renal hypoperfusion, increased sympathetic drive, increased RAAS activity and increased proximal reabsorption of sodium
what blocks the effects of the RAA axis in pregnancy?
progesterone and prostaglandins
how do NSAIDs and COX II inhibitors exacerbate oedema?
block renal prostaglandin synthesis, thereby stimulating sodium reabsorption at the loop of Henle
what does proteinuria with or without haematuria indicate?
renal parenchymal disease
what does haematuria alone indicate?
lesion anywhere along the urinary tract
where are small molecular weight proteins reabsorbed?
proximal tubule
how much protein is contained in normal urine?
<150mg/day
what is the source of the small amount of protein seen in normal urine?
Tamm-Horsfall secreted by the tubule
at what concentration does a dipstick test for protein become positive?
300 mg/L
how much albumin might occur in normal urine?
up to 30 mg
how does vigorous exercise affect proteinuria?
it can transiently increase proteinuria
what are the three components of the normal glomerular capillary wall?
endothelium
glomerular basement membrane
epithelial podocytes
what factors determine the barrier function of the glomerular capillary wall?
intercapillary haemodynamics
negative charge at the epithelial surface slit pores
what maintains the negative charge barrier of the glomerular capillary wall?
glycosaminoglycans such as heparan sulphate and sialic acid
how does vigorous exercise affect erythrocyte excretion?
it may increase transiently
what is the sensitivity of urine microscopy, dipstick analysis and vision for haematuria?
urine microscopy: 0.5x10^6/L
dipstick: 5x10^6/L
naked eye: 5x10^9/L
what are the common causes of non-glomerular haematuria?
urinary tract sepsis
calculi
renal tract tumours
what are the common causes of glomerular haematuria?
IgA disease
thin glomerular basement disease
how is haematuria distinguished from reddish urine caused by free heme pigment?
free heme pigment: negative microscopy, positive dipstick
what is the commonest type of nephrotic syndrome occurring in children?
minimal change disease (followed by focal sclerosing GN)
what is the commonest cause of the nephrotic syndrome in adults?
membranous GN (followed by FSGN)
where does the oedema of nephrotic syndrome initally and then later occur?
initially - subcutaneous tissue
later - serous sacs (pleural, peritoneal fluid)
what are the complications of nephrotic syndrome?
infections
thromboembolic disease
lipid abnormalities
renal failure
what is the only example of direct antibody mediated damage to glomeruli?
anti-GBM disease (Goodpasture's disease)
how does immune complex mediated damage to the glomeruli occur?
via activation of complement and inflammatory pathways
what are the two diseases in which glomerular damage is due to mesangial IgA deposition?
IgA nephropathy
Henoch-Schonlein Purpura
how does damage to the glomerulus occur in vasculitis?
secondary to inflammation occurring within the vascular compartment
t/f... vasculitis is associated with heavy deposition of immunoglobulin and complement seen on renal biopsy
false, vasculitis is associated with a "pauci-immune" pattern
what is seen on electron microscopy in minimal change nephropathy?
fusion of podocyte foot processes
what do the immune deposits in membranous nephropathy usually consist of?
IgG and complement
where are deposits usually found in membranous nephropathy?
subepithelial side of the basement membrane
where are deposits found in post infectious GN?
humps in the subepithelial area
smaller deposits in the mesangium and subendothelial areas
what type of deposits occur in membranous nephropathy?
granular deposits
what causes the damage to the GBM in membranous nephropathy?
complement membrane attack complex
what forms the crescents in rapidly progressive GN?
proliferation of epithelial cells
t/f... rapidly progressive GN typically presents with acute renal failure
true
what are the most common tumours associated with membranous nephropathy?
carcinoma of lung, colon and melanoma
t/f... immune complexes in the glomerulus may be a normal finding
false, they are almost always pathological
t/f... the ductus deferens passes through the prostate
false
what is formed by the ductus deferens and the seminal vesicle to pass through the prostate?
ejaculatory duct
how much fluid is contributed by the prostate?
15-30%
what are the three coverings of the testes that originate from the anterior abdominal wall?
external oblique aponeurosis
internal oblique
transversalis fascia
t/f... the cremaster muscle is skeletal muscle
true
where do the gonadal arteries leave the aorta?
below the renal artery
where do the testicular veins drain?
right - directly into IVC
left - into left renal vein
t/f... the skin of the scrotum has different lymphatic drainage to the testes
true
what is the lymphatic drainage of the skin of the scrotum?
superficial inguinal nodes
what is the lymphatic drainage of the testis?
lateral aortic nodes
what is the thick outer covering of the testes?
tunica albuginea
what are the parts of the epididymis?
head, body and tail
where is sperm produced in the testis?
walls of seminiferous tubules
where is testosterone produced in the testis?
interstitial cells of Leydig
what forms the scrotal septum?
superficial (dartos) fascia
where is the sinus of epididymis?
lateral recess between epididymis and testis
what is the tunica vaginalis?
closed serous sac on anterior surface and sides of each testis and epididymis
what are the contents of the spermatic cord?
ductus deferens, testicular artery, artery of ductus deferens, pampiniform plexus of veins, lymph vessels, autonomic and sensory nerves, genital branch of genitofemoral nerve (supplies cremaster)
what does the ductus deferens do?
carries sperm
t/f... the seminal vesicle is lateral to the vas deferens
true
what part of the prostate is involved in BPH?
transition zone
what zone of the prostate is more commonly involved in cancer?
peripheral zone
what is the venous drainage of the prostate?
mainly internal iliac vein (and internal vertebral venous plexus)
what is the venous drainage of the erectile tissue of the penis?
deep dorsal vein of penis passes inferior to pubic symphysis and drains to prostatic venous plexus
what comprises the root of the penis?
bulb and 2 crura
what comprises the body of the penis?
corpus spongiosum and w corpora cavernosa
what are the three bodies of erectile tissue of the penis?
root
body
glans penis
what is the arterial supply to the penis?
internal pudendal artery
what is the muscle covering the bulb of the penis?
bulbospongiosus muscle
what is the muscle covering the crura of the penis?
ischiocavernosus muscle
when does incontinence occur?
when intravesical pressure exceeds urethral closure pressure
how does detrusor overactivity differ from overactive bladder syndrome?
DO is a urodynamic diagnosis
OAB is a collection of symptoms
what are the symptoms of detrusor overactivity?
motor urgency
what type of urgency occurs with a UTI?
sensory urgency
what is the best treatment of detruosor overactivity?
anticholinergics with bladder training
why is urodynamics indicated in older patients with bladder overactivity before commencement of empirical therapy?
they may have mixed disorders and are more sensitive to side effects
what type of cancer may mimic bladder overactivity?
bladder cancer
what percentage of female incontinence is due to stress incontinence?
30%
what is the definition of genuine stress incontinence and how is it diagnosed?
urethral leakage when intravesical pressure exceeds urethral closure pressure, in the absence of a bladder contraction
diagnosed by videourodynamics
what is the conservative management of stress incontinence?
pelvic floor exercises
reduce abdominal strain (weight loss, reduce cough)
what are the surgical options for stress incontinence?
suburethral sling
pubovaginal sling
t/f... if an older patient presents with nocturnal incontinence, they have bladder overactivity until proven otherwise
false, they have bladder underactivity until proven otherwise
what is the major neurotransmitter involved in erection?
NO
what is the major substance involved in detumescence?
phosphodiesterases
which neurotransmitters are involved in detumescence and flaccidity?
noradrenaline
endothelin
what are the risk factors for erectile dysfunction?
cardiovascular disease
diabetes mellitus
smoking
hypertension
poor general health
psychological and psychiatric disorders
what are the three classifications of organic ED?
vasculogenic
neurogenic
endocrine
what are the contraindications for PDE5Is?
recent MI
angina during intercourse
using nitrates
uncontrolled arrhythmias
what is the best imaging modality for evaluating renal lesions (except renal failure)?
CT
what is the best imaging modality for the evaluation of renal failure?
ultrasound
by how much does a person's risk of prostate cancer increase with a positive family history (one and two first degree relatives)?
one 1st degree relative - x2
two - x9
what findings on PR may indicate prostate cancer?
hard consistency
asymmetry
nodularity
how long should be left before a repeat PSA?
6 wks to 3 months
how long does it take for PSA to drop after infection?
3-6 months
t/f... PSA is highly specific but not very sensitive for prostate cancer
false, the converse is true
what percentage of patients with a PSA between 4 and 10 and a positive rectal examination will have prostate cancer?
30%
what percentage of patients with normal PSA and normal rectal examination have prosate cancer?
2%
t/f... PSA is a good screening test for prostate cancer
false
which free to total PSA ratios are a) suspicious
b) almost never malignant?
a) <10%
b) >24%
what is the positive predictive value for prostate cancer of a positive rectal exam?
6%
what is the positive predictive value for prostate cancer of an elevated PSA?
20%
what is the positive predictive value for prostate cancer of a positive rectal exam and an elevated PSA?
30%
what is the major side effect of transrectal ultrasound biopsies?
infection (risk of E coli infection about 1 in 500)
which gleason score has a better prognosis: 3 + 4 = 7 or 4 + 3 = 7?
3 + 4 = 7
what are the treatment options for T1 and T2 prostate cancer?
watchful waiting
hormonal
radiotherapy
radical prostatectomy
which Gleason scores indicate a patient will probably die from prostate cancer (not with it)?
gleason score > 6
what are the complications of radical prostatectomy?
mortality 0.7%
impotence 30-70%
incontinence 2% severe, 20% mild
bladder neck stricture 5%
bowel injury 1%
what is removed in a radical prostatectomy?
bladder neck, prostate, lymph nodes, seminal vesicles
what is the mainstay of treatment for T3 and T4 prostate cancer?
radiotherapy
what are the complications of radiotherapy?
mortality 0.2%
impotence 42%
incontinence 6%
bladder neck stricture 5%
bowel injury 2%
what is the difference (in terms of complications) between radiotherapy and radical prostatectomy?
radiotherapy - patient develops complications gradually after surgery
radical prostatectomy - patient develops complications straight away but they gradually improve
what is brachytherapy?
implanting radioactive seedlings into the prostate gland
what is the mainstay of treatment for advanced prostate cancer (N and M stages)?
androgen ablation (medical or surgical)
what is the treatment for painful mets of prostate cancer?
radiotherapy
strontium
corticosteroids
palliation
when is prostate development completed?
week 25
where in the prostate does benign prostatic hyperplasia occur?
transitional zone
what are the mechanisms of increased epithelial and stromal cells in periurethral area of prostate gland that occurs in BPH?
epithelial and stromal cell proliferation
impaired apoptosis
t/f... androgens cause BPH
false, there is a permissive but not causative effect
what mediates the conversion of testosterone to dihydrotestosterone in the prostate?
5 alpha reductase
what can cause a partial regression of BPH?
surgical or biochemical castration
pharmacological inhibition of 5 alpha reductase
in what situations will men not develop BPH?
castrated before puberty
5alpha reductase deficiency
what acts synergistically with DHT to produce BPH?
oestradiol
which cells in the prostate produce secretions?
epithelial cells
what percentage of men aged 60 have BPH?
50%
what percentage of men aged 85 have BPH?
100%
how many men aged 85 have BPH requiring surgery?
25%
t/f... the majority of men under 50 with lower urinary tract symptoms have BPH
false, majority have a different cause
what are the two diagnoses important to consider in men with lower urinary tract symptoms?
BPH
OAB
what are the drug therapies for BPH?
herbal remedies (limited quality data)
5 alpha reductase inhibitors (finasteride, dutasteride)
anti-androgens
alpha blockers
how much does finasteride shrink the prostate by?
20%
what are the effects of finasteride?
shrinks prostate by about 20%
modest improvement in LUTS
protective benefits
what improves the efficacy of 5 alpha reductase inhibitors?
concurrent alpha blocker therapy
what are the advantages of minimally invasive therapy for BPH?
better outcomes than drug treatment
low morbidity
more rapid return to normal activities
potential for office based treatment
what are the disadvantages of minimally invasive therapy for BPH?
cost
only modest improvements in symptoms and flow rates
high re-treatment rates
no long term outcome data
what are the complications of TURP?
bleeding (primary and secondary)
infection
incontinence
ED
retrograde ejaculation
urethral stricture
recurrence
what are the common causes of haematuria?
IgA nephropathy
thin membrane disease
trauma
UTI
calculi
neoplasia
BPH
urethral conditions
what is the commonest malignancy in patients with haematuria?
transitional cell carcinoma
what is the strongest risk factor for bladder cancer?
smoking
what are the causes of bladder cancer?
cigarette smoking
exposure to aromatic amines
pelvic radiation
phenacetin
cyclophosphamide
schistosomiasis
what percentage of low grade papillary cancers progress to muscle invasion?
2-3%
what percentage of carcinomas in situ progress to muscle invasive disease?
54%
t/f... BCG is recommended for low grade tumours
false, MMC is recommended
what is the chance of spontaneous passage of kidney stones that are:
>6mm
4-6mm
<4mm?
10%
50%
90%
by how much do STIs increase the risk of acquisition and transmission of HIV?
by a factor of up to 10
what are the four major bacterial STIs?
gonorrhoea
chlamydia
syphilis
chancroid
what are the four major viral STIs?
HIV
HSV
HPV
HBV
what percentage of women with chlamydia and gonorrhoea are asymptomatic?
70%
in what population is chlamydia common?
young people
what are the major manifestations of STIs?
urethral discharge
vaginal discharge
genital ulcers
which STIs may confer infertility?
gonorrhoea
chlamydia
what is the probability of transmitting HIV, gonorrhoea, T palladum and HPV per sexual act?
HIV <1%
gonorrhoea 20-50%
T palladum 20-50%
HPV >60%
what are two physiological causes of vaginal discharge?
menstruation
pregnancy
what are the common vaginal infections causing vaginal discharge?
candidiasis
bacterial vaginosis
trichomoniasis
what are the common cervical infections causing vaginal discharge?
gonorrhoea
chlamydia
what are the causes of urethral discharge?
chlamydia
gonorrhoea
mycoplasma genitalium
ureaplasma urealyticum
other organisms
what are the common infective causes of genital ulceration?
genital herpes
syphilis
tropical STDs
candidiasis
which sites are involved in chlamydia?
male urethra
cervix
what are the complications of chlamydia?
PID
Fitz Hugh Curtis syndrome
epididymo-orchitis
reactive arthritis
how is chlamydia diagnosed?
culture
PCR/LCR
how is chlamydia treated?
azithromycin 1g stat or doxycycline 100 mg bd for 7-10 days
failure to respond - erythromycin 500mg tds for 14 days
what are the sites involved in gonorrhoea infection?
male urethra
cervix
anal canal
throat
what are the complications of gonorrhoea?
PID
Fitz Hugh Curtis syndrome
disseminated infection
epididymo-orchitis
how is gonorrhoea diagnosed?
gram stain and culture
PCR
what can cause ophthalmia nenoatorum?
gonorrhoea
chlamydia
where is gonorrhoea resistant to penicillin?
urban areas
t/f... in rural areas, gonorrhoea is mostly sensitive to penicillin
true
how is the vaginal discharge of candidiasis typically described?
cheesy discharge
what conditions are associated with thrush?
pregnancy
diabetes
what is the discharge of bacterial vaginosis?
frothy offensive vaginal discharge
what causes bacterial vaginosis?
overgrowth of anaerobic bacteria
t/f... bacterial vaginosis is sexually transmitted
false, it is associated with sex
what are the complications of bacterial vaginosis in pregnancy?
low birth weight
prematurity
what are the presentations of trichomonas in men and women?
men - usually asymptomatic
women - frothy vaginal discharge
what are the complications of genital herpes?
urinary retention
meningitis
how is herpes diagnosed?
culture
PCR
serology
which organism causes syphilis?
treponema pallidum
what is the incubation period of syphilis?
9-90 days
t/f... T pallidum is sensitive to penicillin
true
which STD is associated with painful destructive ulcers?
chancroid
which STD is associated with transient genital ulceration and long term lymphatic involvement?
LGV
which STD is associated with beefy, proliferative ulcers?
donovanosis
what is the treatment of most tropical STDs?
azithromycin
where do genital warts occur?
anywhere on the genitals
which strains of HPV tend to cause malignancies?
16/18
what hormonal change occurs at the onset of the first menstrual cycle?
pulsatile spikes of luteinising hormone secreted from anterior pituitary
what are the phases of menstruation?
follicular phase
luteal phase (premenstrual phase)
when in the menstrual cycle does ovulation occur?
day 14
what is the fixed phase of menstruation?
luteal phase (14 days)
what is the acceptable range for length of menstrual cycle?
21-35 days
what is primary amenorrhoea?
no menarche by age 16
what are the most common reasons for late menarche?
high level of exercise
low body weight
genetic
what is secondary amenorrhoea?
no menstrual periods for three months or more
what is oligomenorrhoea?
no period for up to three months
what hormones are involved in the follicular phase of the menstrual cycle?
predominantly FSH producing E2 in ovary
what is the predominant hormone involved in the luteal phase?
LH
progesterone
when in the menstrual cycle are the hypothalamic pulses more frequent and less frequent and which hormones are associated with each frequency?
follicular phase - more frequent pulses favour FSH
luteal phase - less frequent - LH
what is thought to switch FSH to LH production in the menstrual cycle?
progesterone
what are the main regulators produced by the ovary controlling gonadotrophins?
E2
inhibin A and B
where are the inhibins made?
granulosa and thecal cells of mature follicle
how do FSH and LH stimulate the growth of the follicle?
FSH stimulates granulosa cells
LH stimulates thecal cells
what is the action of FSH in the follicle?
convert androgens to oestrogen
what do the thecal cells produce?
androgens
what is the active form of oestrogen?
17beta estradiol (E2)
what is taken up by the granulosa cell and converted by FSH to E2?
androstenedione
what are the E2 and P levels at the end of a menstrual cycle?
low
what inhibits release of FSH and LH?
negative feedback of rising E2
t/f... E2 inhibits release of GnRH
false, it inhibits release of FSH and LH but GnRH continues to stimulate synthesis of FSH and LH which accumulates in the ant pit
what causes the LH surge?
high blood E2 stimulates release of accumulated LH, FSH
what stimulates ovulation?
LH surge
what triggers formation of corpus luteum?
LH
what is released by corpus luteum?
primarily P
E2
what is the effect of E released from granulosa usually and at ovulation?
usually - negative feedback on FSH
ovulation - positive feedback releasing mainly LH
what is necessary to trigger and maintain LH surge?
GnRH
for how long must the LH surge be maintained if corpus luteum is to be formed?
36-48 hours
what causes the degeneration of the corpus luteum?
drop in LH causing a drop in P and E
what is main hormone produced in the luteal phase?
progesterone
what contols the pulses of GnRH?
progesterone
what are the three phases of the endometrial cycle?
proliferative
secretory
menstrual
what is the mechanism of dysmenorrhoea?
increase in free arachadonic acid
stromal cells synthesise and secrete PGF2alpha, PGE2, prostacyclin
what is responsible for the expulsion of menstrual blood?
PGE2 stimulating myometrial contractions
what change in temperature occurs following ovulation?
rise in temperature after ovulation
at what age are contraceptive methods most likely to fail?
<20
how does the OCP affect thromboembolism risk?
oestrogen increases the production of clotting factors (V, VII, X)
which population of women has a 30 fold increased risk of MI?
smokers using OCP
t/f... pregnant women are at a higher risk of thromboembolism than women taking the OCP
true
what is the mechanism of action of copper-bearing IUCDs?
alteration of intrauterine cavity milieu (influx of migratory leukocytes - localised inflammatory process)
milieu is highly hostile to sperm migration through uterus and cervix
in what situations are progestogen only OCPs used?
breastfeeding women
focal migraine
history of thromboembolism
history of MI/cardiovascular disease
underlying coagulopathy (Factor V Leiden)
how does hormonal contraception inhibit ovulation?
suppression of FSH and LH peaks
hypothalamic and pituitary effect
inhibition of follicular development
t/f... the treatment for herpes involves preventing the virus from entering host cells
false, the treatment (nucleoside analogues) acts inside the cell
what type of cells are infected by gonorrhoea bacteria?
polymorphonuclear cells
what aspect of gonorrhoea is a potent stimulator of inflammation?
LPS in cell wall
what is the incubation period of N.gonorrhoea?
1-14 days
which factors influence incubation?
loading dose
host factors
presence or absence of clinical symptoms
what is the risk of a female transmitting gonorrhea from an infected male?
~50%
what is the risk of a male transmitting gonorrhea from an infected female?
20-25%
what is seen on gram stain of urethral exudate with gonorrhea infection?
gram negative intracellular diplococci
what may appear similar to gonococci?
meningococci
what is the best sample from a woman to look for gonorrhoea?
swab of endocervix
what is the disadvantage of diagnosing gonorrhoea with PCR?
don't get any information about antibiotic sensitivity
what does LPS mainly interact with?
C3b (inactivated to iC3b)
t/f... T pallidum organisms are extremely motile
true
which STIs cause cervical infection?
chlamydia
gonnorhoea
which organisms cause vaginal infection?
trichomonas
candida albicans
what is bacterial vaginosis?
imbalance in concentration of normal vaginal flora
which STI has a particular association with PID?
chlamydia
what is Fitz Hugh Curtis syndrome?
perihepatitis associated with gonococcal or chlamydial PID
t/f... the risk of a tubal factor infertility increases after an episode of PID
true
in what type of infection are clue cells present in the vaginal discharge?
bacterial vaginosis
t/f... many chlamydia infections are asymptomatic
true
what are the clinical features of a neonate who has transmitted chlamydia during vaginal delivery?
conjunctivitis
pneumonitis
in which age group is chlamydia commonest?
15-25 years
which STIs are routinely screened for in asymptomatic males and females?
male: gonorrhoea, chlamydia
female: gonorrhoea, chlamydia, trichomonas + endogenous conditions (bacterial vaginosis, candidiasis)
male and female: syphilis, Hep B, HIV, Hep A
what are the causes of urethral discharge and dysuria?
gonorrhoea
chlamydia
T. vaginalis
Mycoplasma genitalis
ureaplasma urealyticum
what are the causes of vaginal discharge?
gonorrhoea
chlamydia
T. vaginalis
C. albicans
BV
what are the causes of genital ulcers?
HSV
syphilis
chancroid
donovanosis
LGV
what is the best investigation for syphilis?
serology
what is pelvic inflammatory disease?
a spectrum of upper genital tract inflammatory disorders among women that includes any combination of endometritis, salpingitis, yubo-ovarian abscess and pelvic peritonitis
what causes PID?
infection by microorganisms that ascend from the cervix or vagina
when is the endocervical mucus plug barrier less protective?
menses
folliclular phase (sex steroid hormone effects)
douching
recent endocervical/uterine instrumentation
recent IUD placement
t/f... currently there are increasing rates of chlamydia infection in Australia but PID is less frequent
true
what are the risk factors for PID?
STI presence
repeat chlamydial infections
young age
coital frequency
contraceptive use
invasive procedures
what are the complications of PID?
subfertility
ectopic pregnancies
chronic pain
other gynaecological morbidity
t/f... gonococcal PID is more likely than chlamydial PID to result in tubal factor infertility
false, the opposite is true
why is chlamydial PID more likely to cause tubal factor infertility than gonococcal PID?
recurrent infections can result in a delayed hypersensitivity reaction with intraluminal scarring and damage
which organism is the cause of most cases of PID in Australia?
chlamydia
what attaches the ovary to the broad ligament?
mesovarium
what attaches the ovary to the uterus?
ovarian ligament
what attaches the ovary to the uterine tube?
one or more fimbriae
where do the ovaries sit in nulliparous females?
ovarian fossa (lateral pelvic wall between ext iliac artery and ureter)
what type of epithelium lines the outer surface of the ovary?
cuboidal epithelium
what contains the ovarian vessels?
suspensory ligament
what is the nerve supply to the ovaries?
plexus on ovarian artery (sympathetic from T10)
reinforced by branches of hypogastric plexus
where does ovary pain refer?
L or R lower quadrant
(may refer to medial thigh - ovary overlies obturator nerve on side wall of pelvis)
what are the parts of the uterine tube from the uterus to the ovary?
uterine
isthmus
ampulla
infundibulum
fimbriae
what is the opening into the peritoneal cavity from the uterine tube?
abdominal ostium
what is salpingitis?
inflammation of the uterine tube
what is the normal location of fertilisation?
ampulla of uterine tube
how thick are the muscular walls of the uterus?
1 cm
what are the internal and external os?
internal os - opening from cervix to uterus
external os - opening from cervix to vagina
what is the perimetrium?
serosal covering of uterus
where does the peritoneum come off the bladder and onto the uterus?
at the junction of the cervix and the body of the uterus
what is the deepest pouch in the peritoneal cavity?
rectouterine pouch (pouch of Douglas)
what is the angle of anteversion?
angle between long axis of vagina and long axis of cervix
t/f... the uterus usually projects into the anterior wall of the vagina
true
what is it called if the uterus projects into the posterior wall of the vagina?
retroversion
what is the angle of anteflexion?
angle between cervix and body of uterus
what guides the descent of the ovary into the pelvic cavity?
gubernaculum
what are the remains of the gubernaculum in the female?
round ligament
ovarian ligament
where does the round ligament lie?
attached to uterus below the uterine tube, passes through inguinal canal to labium majus
what is the mesosalpinx?
part of the broad ligament between uterine tubes and ovary
what is the part of the broad ligament beneath the round ligament?
mesometrium
what is the suspensory ligament?
peritoneum covering ovarian vessels
what provides active support of the uterus?
muscular support - levator ani
what provides poassive support of uterus?
ligaments - pubocervical. transverse cervical, uterosacral
where do the ovarian arteries arise?
from abdominal aorta
what does the ovarian artery supply?
ovary and uterine tube
where do the uterine and vaginal arteries branch from?
internal iliac artery
what is the blood supply to the female external genitalia including erectile tissue?
internal pudendal artery
what are the anterior relationships to the vagina?
bladder
urethra
what are the posterior relationships of the vagina?
rectum
perineal body
t/f... the labia minora contain fat
false
what is the most common cause of commencing end stage kidney disease therapy?
diabetic nephropathy (31%)
(followed by GN - 25%)
what is the most common GN diagnosis?
IgA nephropathy
how many patients with IgA nephropathy have to go onto dialysis?
1/4-/1/3
what is driving the chronic renal failure epidemic?
diabetes
where does functional and structural adaptation to kidney injury occur?
undamaged nephron
what biochemical changes are usually seen in patients with chronic kidney disease?
Na normal
increased K, PO4, Mg
decreased HCO3, Ca
in what order do changes (hyperkalaemia, anaemia, hyperparathyroidism, hyperphosphataemia, acidosis) occur in CKD?
hyperparathyroidism
anaemia
acidosis
hyperkalaemia
hyperphosphataemia
what is the dyslipidaemia that occurs in CKD?
hypertriglyceridaemia
t/f... most patients with CKD will end up on dialysis
false
what do most patients with CKD die of?
cardiovascular complications
what factors are proven to contribute to progression of CKD?
blood pressure
proteinuria
protein and phosphate in the diet
What are the clinical features of PCOS?
Hirsutism, acne, infertility, amenorrhoea, oligomenorrhoea, dysfunctional bleeding
What is the definition of PCOS?
Presence of two of... clinical and/or biochem signs of hyperandrogenism; oligo and/or anovulation; appearance on ultrasound of “polycystic ovaries”; exclusion of other known causes
What are the cysts in PCOS?
Small, immature ovarian follicles
When should the scan be performed for diagnosis of PCOS?
First half of cycle
How many “cysts” are required for diagnosis of PCOS?
12 or more follicles measuring 2-9mm in diameter
By how much is ovarian volume increased in PCOS?
>10cm^2
Which cells of the follicle make oestrogen?
Granulosal cells
What surrounds the granulosal cells?
Thecal cells
What do the thecal cells do?
Convert cholesterol to testosterone (via progesterone)
Which follicle cells convert testosterone to oestradiol?
Granulosal cells
Which hormones cause thecal cells to proliferate in PCOS?
LH, insulin
What is the main hormone product of the follicle in PCOS?
Testosterone
Why is testosterone the main hormone product of the follicle in PCOS?
Thecal cells are more numerous in PCOS
What does the excess testosterone do in PCOS?
Passes through basement membrane into follicle and inhibits growth of follicle
Where are the immature follicles located in PCOS?
Edge of ovary
What causes the hirsutism and acne of PCOS?
Excess testosterone
What causes the irregular/heavy bleeding in PCOS?
Follicles are producing oestradiol (stimulating thickening of endometrium) but no ovulation occurs so no progesterone is released
Which hormone stimulates ovulation?
LH
What causes the increased LH concentration in PCOS?
Prolonged exposure to unopposed oestradiol – increased GnRH pulse frequency
Antenatal programming
Why is the insulin concentration increased in PCOS?
Obesity, insulin resistance, androgen effect in utero
How is PCOS hirsutism treated?
Anti-androgen or 5-alpha reductase inhibitor
How is irregular/heavy bleeding treated in PCOS?
Progestogens or OCP
How is anovulation treated in PCOS?
Anti-oestrogens or aromatase inhibitor
What is a very important concern in treating PCOS with anti-androgen or 5 alpha reductase inhibitor?
The patient must not become pregnant as the male foetus requires testosterone for virilisation in utero
What are the side effects of clomifene citrate?
Hot flushes, headaches
In what percentage of patients treated with clomifene citrate is ovulation induced?
70%
What percentage of patients with PCOS treated with clomifene citrate achieve pregnancy?
30-40%