renal physiology W1 Flashcards
how does the macula densa interact with the rest of the body?
JG cells release renin
what is renin
a protease!
what causes JG cells to release renin
macula densa cells pump out more NaCl than usual
baroreceptors in JGA respond to elevated glom bp
what does renin convert?
angiotensinogen -> angiotensin I
what converts angiotensin 1 to angiotensin 2? where?
ACE (angiotensin converting enzyme) on surface of pulmonary and renal endothelium
what does angiotensin 2 stimulate?
sympathetic activity
arteriolar vasoconstriction (increase in bp)
salt resorption in kidney tubules
secretion of aldosterone from adrenal gland
secretion of AVP from posterior pituitary
how does angiotensin 2 stimulate salt resorption in kidney tubules?
binds to receptor in the proximal convoluted tubule, this increases the activity of the Na+/H+ exchanger.
leads to more sodium uptake.
action of aldosterone on kidney cells?
affects gene transcription (as it is a steroid)
affects 2 different cells in collecting duct:
coll duct principal cell (most common): affects 2 genes
causes Na+/K+ and ASC expression
coll duct alpha-intercalated cell:
gene expression of H+ channels that allow exit from the cell without K+ (which is required in absence of aldosterone)
affect of AVP on kidney cells? (aka ADH/vasopressin)
in collecting duct, causes aquaporin to move from vesicles to membrane which allows water uptake (elevating bp)
end results of RAAS system?
increase in BP!! (due to…)
water and salt retention!
effective circulating volume increases. perfusion of the juxtaglomerular apparatus (JGA) increases
affect of increased sympathetic activity caused by angiotensin 2 on the kidneys?
sympathetic renal nerves secrete noradrenaline, constricts both afferent and efferent arterioles so reduces flow (therefore reduced filtration, therefore reduced water loss). also directly promotes renin release
when is ANP produced and what does it block?
produced when bp is too high. blocks activity of RAAS.
parathyroid hormone response to Ca+ in blood?
parathyroids respond to low blood Ca+ by secreting parathyroid hormone (PTH) which acts on the kidney
actions of PTH on the kidney? (overall picture)
increased Ca2+ recovery in distal collecting duct
decreased phosphate recovery in proximal convoluted tubule
actions of PTH in distal collecting duct?
calcium uptake through channel (activated by PTH), binds to calcium binding proteins (eg calbindin). takes calcium to exit channel (activated by PTH).
what components in the calcium path in the kidney require vitamin D? what through this pathway can vitamin D deficiency lead to?
calbindin
calcium exit channel into body
vit D deficiency leads to rickets due to this pathway
actions of PTH in the proximal tubule?
inhibition of sodium and phosphate cotransporter (prevents uptake)
this increases free calcium ions as calcium can either be a free ion in the blood or circulate as calcium phosphate
fall in intracellular pH causes what?
apical Na+/H+ exchangers more active (Na+ in, H+ out)
H+ excreted (complexed with buffers once in urine)
potassium in alkalosis?
H+ out pumping by intercalated cells reduced, so less K+ reuptake (and apical K+ channel activity increased in principal cells and so is the Na+/K+ ATPase -> more K+ loss.
—-> hypokalaemia
potassium in acute acidosis?
H+ out-pumping by intercalated cells increases so K+ reuptake increases. Also, apical K+ channels on Principal cells less active (by an effect on their intracellular regulation) so K+ secretion falls.
—-> hyperkalaemia
what does aldosterone drive in terms of K+?
export out of the body in some cells, non recovery in others
4 causes of clinical intervention in renal function?
control of oedema (in this lecture)
control of hypertension (in this lecture)
control of ion imbalances
control of acid-based disturbances
what is diuresis?
(eg what is the effect of diuretics)
increasing the amount of water (+ salts) lost from the body (if you lose them together, you don’t mess up plasma salinity)
action of loop diuretics?
block 2Cl-/K+/Na+ uptake channel.
this stops area of kidney medulla being salty, therefore stopping the drive of water resorption
increases urine output!
loop diuretics features
powerful!
result in loss of Na+, K+, and Cl+ because of failure to recover
the inhibit Na uptake in the macula densa (uses same channel)
can result in hypercalcuria (due to less pull for calcium recovery because it follows other ions) and kidney stones
more Na+ getting to collecting duct, meaning more uptake and more K+ loss
why is loop diuretics inhibiting sodium uptake in the macula densa a bad thing?
inhibiting salt uptake at macula densa makes kidney think there’s hardly any salt in the urine. concludes bp must be low for the flow to be this low, therefore increases renin (which increases bp, opposing our attempts to lower it)
what conditions are loop diuretics good and bad for?
good for oedema
bad for hypertension
thiazides mechanism of action?
thiazides - target channel in distal tubule that uptakes Ca- and Na+, causing reduced salt uptake and water recovery. the macula densa isn’t affected
also seem to directly affect vascular tone (reduce bp)
thiazides and the macula densa?
macula densa is before thiazides cause there effect, therefore isn’t affected
potassium sparing diuretics mechanism of action?
act on ASC (amiloride sensitive sodium channel) in collecting duct to prevent uptake of Na+
happens after macula densa so no effect there
example of potassium sparing diuretics?
amiloride
what drug affects aldosterone action? mechanism of action?
spironolactone blocks action of aldosterone (which activated transcription of the gene which coded for the ASC)
therefore reduces sodium uptake
problem with spironolactone?
in males - antiandrogenic hormone, competes with eg dihydrotestosterone therefore affects normal signalling, pushes body into female type development (can get gynaecomastia - formation of female breast on male body)
therefore not usually prescribed to males
carbonic anhydrase inhibitors?
block carbonic anhydrase, blocks bicarbonate recovery. urine more concentrated than it would be, so less of an osmotic pull to take water and other things into body.
osmotic agents?
molecules that irreversibly filter from blood to urine.
make urine more concentrated than it would be otherwise, reducing concentration differences between urine and body space, therefore reduce water reuptake.
summary of site of action of different diuretics?
carbonic anhydrase inhibitors - PCT
loop diuretics - LoH, col duct
thiazides - DCT
amiloride and spironolactone - ASC in col duct
