Wednesday, August 18, 2010

CONSULT ROUNDS: LOW POTASSIUM STORY!

When you encounter a hypokalemia with metabolic alkalsosis that is normo-tensive, there are very few diagnosis to consider: Diuretic use, abuse or diuretic like syndromes ( namely Bartter Syndrome(BS) and Gitelman's Syndrome(GS))
Take home points:
1. There are 4 different types of Bartter syndrome( basically anyway the cell in the thick ascending loop of henle can be affected in absorption of Na-Cl.)- a loop diuretic like effect


Bartter syndrome I - Defects in the Na-K-2Cl transporter
Bartter syndrome II - Defects in the apical potassium channel, caused by mutations in the ROMK1 gen
Bartter syndrome III - This is due to mutations in the CLCNKB gene leading to Cl channel problem in the basolateral surface.
Bartter syndrome IV - This is due to mutations in the CLCNKA gene. Again affecting the Cl-K exchange in the basolateral surface.
2. A fifth variant might occur that is AD as opposed to being AR (the above 4 variants) that affects the Ca sensing receptor in the basolateral surface.
3. Most of the above lead to hypocalcemia and hypercalciuria.  
4. Gitelman's syndrome is a loss-of-function mutations in the SLC12A3 gene that codes for the thiazide-sensitive Na-Cl cotransporter in the distal convoluted tubule. This leads to a more pronounced hypomagnesemia and hypocalciuria compared to the prior. This is a more common entity in adults
5. An interesting way to differentiate the two would be to use diuretics to observe the Urinary Cl and Na concentrations. A patient with GS, when given Thiazides will have no major change as that channel is already not working but will have an increase in Urinary CL and Na when given a Loop diuretic. Vice versa, the effect of loop of a patient with BS will show no changes but when given a thiazide will have increase urinary CL and Na.
6. Treatment is usually using K sparing agents like Amiloride, aldosterone antagonists or NSAIDs.
7. Chronic Hypokalemia can lead to hypokalemic related Nephropathy and ESRD.
8. Renin and Aldosterone levels are usually high in these cases.


Few good references regarding the use of diuretics to make diagnosis
http://www.ncbi.nlm.nih.gov/pubmed/17699451
http://www.ncbi.nlm.nih.gov/pubmed/1731022
http://www.ncbi.nlm.nih.gov/pubmed/12172059

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