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michigan hypertension core curriculum - State of Michigan

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intake. 4<br />

Figure 1;<br />

Ion transport in collecting tubule cell<br />

Schematic representation <strong>of</strong> sodium and potassium transport in the sodium reabsorbing cells in the<br />

collecting tubules. The entry <strong>of</strong> filtered Na into the cells is mediated by selective sodium channels in<br />

the apical (luminal) membrane; the energy for this process is provided by the favorable electrochemical<br />

gradient for Na (cell interior electronegative and low cell Na concentration). Reabsorbed Na is pumped<br />

out <strong>of</strong> the cell by the Na-K-ATPase pump in the basolateral (peritubular) membrane. The reabsorption<br />

<strong>of</strong> cationic Na makes the lumen electronegative, thereby creating a favorable gradient for the secretion<br />

<strong>of</strong> K into the lumen via K channels in the apical membrane. Aldosterone, after combining with the<br />

cytosolic mineralocorticoid receptor (Aldo-R), leads to enhanced Na reabsorption and potassium<br />

secretion by increasing both the number <strong>of</strong> open Na channels and the number <strong>of</strong> Na-K-ATPase pumps.<br />

Atrial natriuretic peptide, on the other hand, acts primarily in the inner medullary collecting duct by<br />

combining with its basolateral membrane receptor (ANP-R) and activating guanylate cyclase. ANP<br />

inhibits sodium reabsorption by closing the Na channels. The potassium-sparing diuretics act by closing<br />

Na channels, amiloride and triamterene directly and spironolactone by competing with aldosterone.<br />

Used with permission from Dr. Raymond Townsend @ Uptodate<br />

Diagnosis and Evaluation<br />

Recent guidelines published by the Endocrine Society in 2008 detail the evaluation <strong>of</strong> PA.<br />

(Figure 2) The first test is the plasma aldosterone /renin ratio (ARR), preferably performed the morning.<br />

This screening test has both false positives and false negatives. Although many antihypertensives can<br />

affect levels <strong>of</strong> renin and aldo, only two render the test uninterpretable. The test must be performed<br />

in patients who have not taken either an aldosterone antagonist or a renin inhibitor within the<br />

past 4-6 weeks. A positive screen consists <strong>of</strong> an aldosterone level > 14 ng /dl (416 pmol/l), with a PRA<br />

less than 1 ng /ml/hr (12.8 pm/l in SI units); nevertheless, a not inconsequential proportion <strong>of</strong> patients<br />

with PA will not have circulating aldosterone levels > 14 ng/dl. PRA is now being performed in some<br />

laboratories as a direct renin concentration or DRC, which requires conversion. Knowing local values<br />

100 Hypertension Core Curriculum

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