Sweep 1.2 Flashcards
K+ - sparing diuretics act where
K+ is normally secreted into the tubular fluid by the principal cells.
K+ sparing
- aldosterone antagonists,
e.g. spironolactone
block aldosterone’s ability to increase Na+ transporters in principal cells
must get inside tubular cells to block aldosterone receptors
K+ sparing
2. ENaC blockers,
e.g. amiloride
block Na+ reabsorption across the apical membrane
these act on a membrane protein so can gain access by secretion into the proximal tubule
Aquaretics, e.g. tolvaptan, increase excretion of
water by blocking the action of ADH in the late distal tubules and collecting duct. Water is eliminated without the loss of solutes.
Diuretic braking phenomenon
Continued use of diuretics becomes
less effective because volume contraction counteracts the effects of the diuretic, i.e. diuretics decrease ECV so compensatory mechanisms activated
- increased sympathetic activity in response to reduced BP –> decrease —– —-> increase
GFR
PT reabsorption & increase renin
Secondary effects of diuretics
2. decrease
natriuretic peptides
Increased excretion of K+
Diuretics increase ——–, so they secondarily influence renal processing of other solutes (and water)
Na+ reabsorption
K+ excretion increases because……
diurectics increase the flow of tubular fluid which stimulates K+ secretion
diuretics reduce ECV à increase aldosterone à stimulate K+ secretion
K+ -sparing diuretics are used to prevent an increase in K+ secretion
Loop and thiazide diuretics —>
reduced ECV à metabolic alkalosis
potassium-sparing diuretics —–> ———- because H+ secretion in distal tubule and cortical collecting duct is -=——
metabolic acidosis
inhibited
Except for ———-, all other diuretics alter calcium excretion.
the K+ sparing diuretics
Calcium reabsorption in the nephron
in proximal tubule –
mostly by paracellular transport/solvent drag
Calcium reabsorption in the nephron
in thick ascending limb –
transcellular and paracellular transport (paracellular not solvent drag)
Calcium reabsorption in the nephron
in distal tubule –
transcellular reabsorption of calcium
transport here can be regulated because expression of Ca2+ transporters is regulated by PTH
Calcium reabsorption in the nephron
the collecting duct is not significantly involved with
Ca2+ reabsorption
• calcitonin
released in response to ———-
increases ————
hypercalcaemia
bone deposition
• calcitriol (1,25 dihydroxyvitamin D)
metabolism of vitamin D to calcitriol is stimulated by
hypocalcaemia and/or hypophosphatemia (and further stimulated by PTH, see above)
• calcitriol (1,25 dihydroxyvitamin D)
stimulates active transport mechanism for
Ca2+ absorption in the small intestine
• calcitriol (1,25 dihydroxyvitamin D)
facilitates action of ——- and increases ——
PTH
renal Ca2+ transport
• parathyroid hormone (PTH)
released in response to
hypocalcaemia
• parathyroid hormone (PTH)
increases ———–, increases renal —– reabsorption, and stimulates ——–
bone resorption
Ca+
calcitriol production
Calcium is regulated by three hormones all of which are regulated by a
calcium sensing receptor (CaSR)
Osmotic and CA inhibitors both act in ——— and reduce reabsorption of ————
proximal tubule
calcium in this segment (so excretion is increased).
Loop diuretics increase calcium excretion by affecting the
transepithelial voltage that normally provides the driving force for paracellular transport of calcium.
Thiazide diuretics stimulate
calcium reabsorption in the distal tubule and thus reduce excretion.
Normally, distal tubule reabsorbs —- of filtered calcium via active transport.
9%
catheter – used to access
venous blood for short-term treatment; scarring, vessel narrowing or occlusion can occur
AV fistula – preferred for
long-term treatment; creates an anastomosis between artery and vein. Arterial blood is withdrawn, and blood is returned to the vein after dialysis.
AV graft – uses an
artificial/synthetic vessel to join an artery and vein when vascular problems do not permit using a fistula; can become narrowed which can lead to clotting and/or infections.
Long-term consequences of hemodialysis
sepsis, endocarditis & osteomyelitis (secondary infections)
amyloid deposits in joints (like amyloid plaques that form in neural tissue) can result from the build-up of trace minerals (e.g. copper, zinc, and aluminum) that might be in the dialysis fluid.
Patients with chronic renal failure are almost always diagnosed with
anemia due inadequate secretion of erythropoietin (EPO) and loss of erythrocytes.
EPO is produced by ———— in the renal cortex, and its production is controlled at the transcriptional level.
interstitial fibroblasts
HIFs are continually produced, but are targeted for degradation when
O2 is normal.
HIFs
When O2 is low, they function as
transcription factors to increase EPO synthesis and secretion.
EPO stimulates differentiation of ——— in the bone marrow
erythrocyte progenitor cells
transcellular – molecules move
through tubular cells
paracellular – molecules move
between tubular cells
solvent drag results from solutes being carried by water in
paracellular transport
rate of water diffusion can be regulated by
aquaporins
Note that a decrease in plasma pH will increase the amount of ———- which can be filtered and excreted, so alkalosis can lead to ———-.
free Ca2+
hypocalcemia
Why is it important to regulate calcium?
hypocalcemia increases
excitability of neural and muscle tissue; tetany
Why is it important to regulate calcium?
hypercalcemia can cause
cardiac arrhythmia and disorientation; can lead to death
only a little more than ½ of ECF calcium is
free or complexed with anions, and, therefore, can be filtered in the glomerulus
Metabolic alkalosis – hi
pH due to excess HCO3-
Metabolic alkalosis
respiratory compensatory response –
hypoventilate (how does this work?) – increase CO2, increase CA reaction, increase acidity
Metabolic alkalosis
renal compensatory response —>
excrete HCO3-
Metabolic acidosis - low pH due to low
HCO3-
Metabolic acidosis
causes include
diabetic ketosis, diarrhea, renal failure
Metabolic acidosis
respiratory compensatory response —->
hyperventilate
Metabolic acidosis
renal compensatory response —> produce
new HCO3-
