Diuretics Flashcards
what makes up renal corpuscle?
glomerulus
bowman’s capsule
what are the types of nephron?
cortical nephrons
juxtamedullary nephrones
depends on how deep they go into the nephron
function of glomerulus
filter fluid and small molecules
function of PCT
split into piles convoluter and piles recta
major absorption and secretion
function of LoH
generating hypertonic interstitium in medulla
salt absorption
function of DCT
fine tuning
additional absorption and secretion
macula densa
function of macula densa
detects salt and filtrate production and triggers juxtaglomerular cells to produce renin
collecting fuct
collects filtrate
hormone sensitive
to adjust salt and water movement
aldosterone and ADH affect it
what are the classes of diuretics?
osmotic carbonic anhydrase inhibitors loop diuretics thiazide-like diuretics potassium sparing diuretics
osmotic diuretics
simplest
filtered into tubules and not reabsorbed so increase osmolality of tubules so draws water into the tubules
osmotically active molecules are filtered out of the glomerulus
increases net H2O loss
e.g. of osmotic diuretics
mannitol - sugar
for cerebral oedema
carbonic anhydrase inhibitors
complex mechanism
PCT
carbonate and H+ combine to form bicarbonate and then forms H2O and CO2 due to carbonic anhydrase
CO2 and H2O enter the cell paracellularly
inside the cell carbonic anhydrase then converts it back to HCO3- and H+
HCO3- is reabsorbed
protons are needed inside the cell for anti-porter to reabsorb Na+
inhibiting carbonic anhydrase reduces H+ movement in filtrate and reduces sodium reabsorption
increases filtrate osmolality and causes H2O
principal behind carbonic anhydrase inhibitors
inhibit recycling of bicarbonate
reducing Na+ reabsorption
e.g. of carbonic anhydrase inhibitors
acetazolimide
not used for oedema
clinically minor effect
what are carbonic anhydrase inhibitors used for?
altitude sickness
glaucoma
where do Loop diuretics work?
act at LoH
thick ascending limb
epithelial of thick ascending limb of LoH
cuboidal
epithelial of thin ascending limb of LoH
squamous
how do loop diuretics work?
NKCC as ascending LoH where 25% of Na+ is absorbed
these inhibit the NKCC sympoter on the apical/ luminal side
Na+ accumulates in tubule - water cannot follow as the ascending LoH is impermeable to water
increases osmotic gradient for water loss later on in the nephron - DCT and collecting duct
apical side
side of epithelial cell facing tubules
basolateral side
side of epithelial cell facing blood vessels
e.g. of loop diuretic
furosemide
use of loop diuretic
oedema
meniscus and fluid under left hemidiaphragm
gastric bubble
where do thiazide-like diuretics work?
DCT - only 3% Na+ reabsorbed
thiazide-like diuretics
DCT becomes more water permeable proximally to distally
these diuretics block NaCl symporter on apical side
retains Na+ in tubule
reduces reabsorption of water
movement of water into tubules
to maintain Na+ levels in cell Na+/Ca2+ exchanger increases moving more Na+ from the blood into the cell and Ca2+ into the blood - risk of hypercalcaemia
hypercalcaemia with thiazide like diuretics
normally not a problem because calcium homeostasis negates the effect
but can be a problem for people with certain conditions related to calcium homeostasis
e.g. of thiazide-like diuretics
indapamide
thiazide molecules are not longer used due to high side effect profile - hyponatraemia
uses of thiazide-like diuretics
step 3 antihypertensives
not that effective as diuretics
decrease sensitivity of smooth muscle in vasculature to circulating vasoconstrictors
kidney stones and thiazide-like diuretics
calcium increased in blood by thiazide-like diuretics
so can protect patients from kidney stones because calcium is transported into the blood not urine
diuretics
most increase risk of kidney stones, except thiazide-like diuretics
where do potassium sparing diuretics act?
principal cell of collecting duct
side effect of loop diuretics and thiazide-like diuretics?
hypokalaemia, only potassium-sparing diuretics do not increase K+ loss
what is the responsibility of intercalated cell?
acid/base balance
what are the types of potassium sparing diuretics
aldosterone antagonists
non-mineralocorticoid antagonist
how do non-mineralocorticoid antagonist K+ sparing diuretics work?
inhibit Na+ channel - ENaC on apical membrane so Na+ accumulates in the tubule
how do aldosterone antagonist K+ sparing diuretics work?
block the effect of aldosterone which causes protein synthesis of ENaC and Na+/K+ pump so reduces the amount of these present
where do aldosterone antagonist K+ sparing diuretics work?
act on nuclear receptors
act on apical and basolateral side of epithelial cells
e.g. of aldosterone antagonist K+ sparing diuretics work
spironolactone
eplerenone
use of aldosterone antagonist K+ sparing diuretics work
reduced cardiac remodelling
use in heart failure with reduced ejection fraction
poor antihypertensive if nothing else has worked
may be used as diuretic in those with oedema caused by cirrhosis
when is spironolactone used?
potassium retention
used with other diuretics to spare potassium
can caused breast tissue development in men
