diuretics and metabolic alkalosis

[ketap]

hello..i want to ask : how can diuretics (such as thiazide and furosemide) cause metabolic alkalosis? i 've heard that it is because they loss the chloride too much....i don't really understand this..when they block their site of action, they will deliver high NaCl to the distal tubule and then the aldosterone will reabsorb the Na and the body will loss the potassium in exchange...if the sodium is reabsorbed, than doesn't an equal Chloride should be reabsorbed as well? if it is, so how can the diuretic cause the metabolic alkalosis? or am i wrong about it and they loss more chloride than the sodium?thx u

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[Phlame217]

You're right up to the deliver of NaCl to the distal tubule.

Theres a Aldosterone controlled Na/K pump there. Pump Na into the cell from the lumen and pump K from the cell into the lumen. If the kidney were to run low on K, it can substitute Hydrogen for K+. However, the cell must produce the hydrogen to pump out. So it splits water and carbon dioxide into Hydrogen and Bicarb (generating new bicarb).

Bicarb gets pumped into the blood, Hydrogen into the lumen in exchange for Na. Hence, you get Met Alkalosis.

 

[MrBigglesworth]

1,) Low volume causes an increase in aldosterone. Aldosterone's effect on the intercalated cell is to pump out an H+ = increase pH.

2.) Low K+ causes a transcellular shift for hydrogen ion. K+ leaves cell and H+ enters the cell = decrease plasma H+ = increase pH.

 

[AndyRSC]

Everything MrBigglesworth said, plus:

3. Loss of bicarbonate-poor, chloride-rich extracellular fluid, as observed with thiazide diuretic or loop diuretic therapy or chloride diarrhea, leads to contraction of extracellular fluid volume. Because the original bicarbonate mass is now dissolved in a smaller volume of fluid, an increase in bicarbonate concentration occurs.

4. Loss of chloride-rich fluid leads to enhanced bicarbonate reabsorption. In the late thick ascending limb and early distal tubule, specialized cells called the macula densa are present. These cells have an Na+/K+/2Cl- cotransporter in the apical membrane, which is mainly regulated by chloride ions. When fewer chloride ions reach this transporter, the macula densa signals the juxtaglomerular apparatus to secrete renin > angiotensin II > aldosterone. #1 is enhanced.

5. Furthermore, the kidneys secrete the excess bicarbonate via the apical chloride/bicarbonate exchanger in the B-type intercalated cells of the collecting duct. In this way, protons are gained to the systemic circulation via the basolateral H+ ATPase. In chloride depletion, fewer chloride ions are available to be exchanged with bicarbonate, and the ability of the kidneys to excrete the excess bicarbonate is impaired.

 

[ketap]

hi,thx for answering,friends....i am sorry if i bother u but i have question again..:

Loss of bicarbonate-poor, chloride-rich extracellular fluid, as observed with thiazide diuretic or loop diuretic therapy or chloride diarrhea

1. now ,this is my confusion..how can a diuretic cause higher Cl- loss than the HCO3 loss (bicarbonate- poor , chloride- rich fluid ) ?

2. mentioning about the volume contraction : i just want to clarify , so a patient with a volume depletion will have metabolic alkalosis only if he has bicarbonate- poor , chloride- rich fluid loss but not if he has the equal HCO3 - Cl fluid loss, right?

thx u

best regards,Ketap

 

[Oh_Gee]

how is chloride lost?

 

[Herobiro]

by thiazides blocking Na Cl channels in DCT .. or loops blocking Na k 2Cl channels.