Site 1 diuretics
Carbonic Anhydrase inhibitors - Na, Cl, HCO3 stay in lumen along with water. side effect = metabolic acidosis (HCO3 lost in urine = not reabsorbed into blood) Used as prophylaxis for acute mountain sickness (metabolic acidosis counters the respiratory alkalosis from hypoxia induced hyperventilation) and to reduce aquaeous humor formation in eye (glaucoma)
Site 1-5 osmotic diuretics; e.g., mannitol - volume expansion of ECF leads to decreased renin secretion = decreased aldosterone = Na loss H2O loss.
Site 2 - loop diuretics - most potent - prototype furosemide (lasix). decreased Na delivery to macula densa (turns off tubuloglomerular feedback). Inhibit Na, K, Cl tri-transporter. hypokalemia causes metabolic alkalosis - and enhances digitalis toxicity.
Site 3 (distal tubule) - thiazides. increased excretion of NaCl. "low ceiling = limited volume loss". inhibit Na-Cl symporter in DCT. hypokalemia; hypercalcemia (reduced Ca secretion)
"Thiazides INCREASE calcium reabsorption. Two mechanisms have been proposed for this effect. Thiazide blockade of the sodium-chloride-cotransporter in the distal tubule leads to volume depletion and elevates passive transcellular calcium and sodium reabsorption from the proximal tubule. In addition, increased sodium delivery to the late distal tubule appears to increase calcium reabsorption in the late distal tubule. Together, these effects can lead to a significant reabsorption of filtered calcium. This is opposite to the effects of the loop diuretics, such as furosemide which tend to cause calcium wasting. For that reason, the two classes of drugs have opposite effects on the formation of kidney stones with thiazides decreasing the frequency of stone formation and loop diuretics increasing the risk."
Site 4 (late distal tubule and collecting duct). inhibit epithelian sodium channels (ENaC) = countering aldosterone; e.g. amiloride. Potassium sparing diuretic. Hyperkalemia causes metabolic acidosis. blocking aldosterone also causes metabolic acidosis directly. Aldosterone antagonists; e.g., spironolactone. anti-androgenic effects.
Site 5 - vasopressin (V2) blockers - increase urine volume.
http://www.cvpharmacology.com/diuretic/diuretics.htm
Danielson
pHa < 7.35 = acidemia pHa > 7.45 = alkalemia
...osis versus ...emia. acidosis is a condition due to respiratory or metabolic change. initially causes acidemia but later pH may be compensated back to within normal range (called compensated acidosis). Similar for alkalosis.
metabolic acidosis = low pH due to low HCO3. caused by addition of acid or loss of HCO3 (e.g., diarrhea). Winter's formula for expected PCO2 compensation. expected PCO2 = 1.5 x HCO3.
"make it or take it" make it = daily acid load from metabolism. CO2 load =
metabolic alkalosis = high pH due to high HCO3. causes = gastric suction. vomiting. diuretics (contraction alkalosis).
ROME ( "respiratory opposite; metabolic equal) describes pH change with PCO2 change (respiratory) and pH change with HCO3 change (metabolic).
Anion Gap (AG) = unmeasured anions (mainly albumin). Na+ - HCO3 - Cl = AG.
E-MUDPILES
Normal anion gap with metabolic acidosis (hyperchloremic metabolic acidosis).
diarrhea; renal tubular acidsosis, CA inhibitors; HCl ingestion.
Osmolar Gap = measured serum Osm - calculated serum Osm. increases with increased serum solutes or ethanol, methanol.
http://www.anaesthesiamcq.com/AcidBaseBook/ab3_5.php
Main Use of Osmolar gap:
Screening test for detecting abnormal low MW solutes (esp ethanol, methanol & ethylene glycol
Fisher
proteinuria due to foot process effacement so more prevalent in nephrotic syndrome than in nephritic syndrome.
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