Loop-de-loop of Henle Loop Diuretics

2.2 – “Loop “Loop-de-de-de-loop loop of Henle”: Loop Di Diuretics uretics (furosemide, et ethacrynic hacrynic ac acid) id) • Loop diuretics are extremely potent diuretics that affect the ascending Loop of Henle (LOH) (nephron map. riders ascending the loop). Produce rapid diuresis & fluid loss. Loop of He Henle nle physiology • The thick ascending limb (TAL) is impermeable to water; only solutes are resorbed here (water in carts is security. Causes dilution of tubular fluid. Crucial to maintain renal hypertonicity that allows for water resorption further along in the collecting ducts. In all, 25% of filtered sodium is resorbed in the TAL. • Na-K-ATPase pumps on the basolateral membrane (i.e. the intracellular compartment of the tubular epithelial cells [platform of the ride]) maintain a low intracellular sodium concentration to enable absorption from the lumen (salty peanuts at the banana vending machine; lumen = yellow track). • Na/K/2Cl cotransporter (NKCC) at the luminal membrane of resorbs the eponymous ions (no food allowed on the luminal ride). Note that this ion combination is electrically neutral. • While the NKCC transporter is itself electrically neutral, action contributes to excess K accumulation in the cell. K diffuses back into channel via ROMK channel, producing a positive luminal electric potential which allows for cation resorption, including Ca & Mg. Loop diuret diuretics ics • Include furosemide (furious kid) & ethacrynic acid (code of ethics sign) • Loop diuretics function by inhibiting the NKCC. Net effect is to impede sodium absorption in the ascending limb. ↓NaCl resorption → natriuresis. Not limited by the acidosis seen with acetazolamide. • Loop diuretics induce expression COX-2 → prostaglandin synthesis (pro-slugger bat). Prostaglandins dilate the afferent arteriole and enhance salt excretion, resulting in increased solute delivery to nephron, increasing loop diuretic efficacy. o NSAIDs can interfere with the action of loop diuretics by decreasing prostaglandin synthesis (fire extinguisher blocking baseball bat kid) • Indications: o First line for symptomatic treatment of acute decompensated HF with fluid overload (guy with lung-shaped vest & failing heart balloon) ▪ HF → hypoperfusion of kidneys → upregulation of RAAS, which causes fluid retention. ▪ Loops help with maximum diuresis in shortest time (#1 balloon) ▪ Particularly helpful with pulmonary edema (guy with wet lung-shaped life vest) ▪ Removing venous overload can help with ↓preload, preventing overfilling and increasing cardiac efficiency ▪ Do not have any effect on M&M. are symptomatic control only o Treatment of HF, particularly when there are comorbidities. ▪ Especially useful in cases of severe HTN (high pressure pipes), renal insufficiency, cirrhosis, or cardiac failure. o Treat ascites in liver failure (gal with yellow innertube). Can be useful when peripheral ascites and edema worsen in liver failure. • Side effects/toxicities o Potassium wasting. Can cause hypokalemia (banana peel falling). Must monitor potassium. Note this can exacerbate HF. o Loop diuretics cause decreased cation resorption d/t disruption of the luminal electric potential . In particular, calcium and magnesium will remain in the lumen, resulting in hypomagnesemia and hypocalcemia. (Kid on ride clinging to magnesium magnets & calcium ice cream; other kid with falling magnets & ice cream). Hypomagnesemia can be reversed by oral magnesium); hypocalcemia is rare d/t maintenance by other physiologic mechanisms including Vitamin D induced intestinal absorption & PTH-induced renal resorption. o May occasionally cause dose-related hearing loss (gong). Usually reversible with treatment cessation. o May rarely see interstitial nephritis with loop diuretics (kidney-shaped bucket filled with little blue tickets) o May cause hyperuricemia, relatively commonly (girl knitting with yellow yarn). Excessive use of diuretics → enhanced uric acid resorption in the PCT with hypovolemia. o Loop diuretics prevent salt reabsorption and therefore prevent water reabsorption, which may cause contraction alkalosis & dehydration (contracted bleach bottle). ▪ Former d/t many mechanisms including hypovolemia induction of RAAS. This ↑angiotensin-II which works directly on Na resorption in PCT. o Furosemide is a sulfa drug, so may see sulfa allergy (throwing eggs). ▪ Can be avoided by using ethacrynic acid (Ethics sign “be sulfa-less”).