Chapter 046. Sodium and Water (Part 17)

Decreased aldosterone synthesis may be due to primary adrenal insufficiency (Addisons disease) or congenital adrenal enzyme deficiency (Chap. 336). Heparin (including low-molecular-weight heparin) inhibits production of aldosterone by the cells of the zona glomerulosa and can lead to severe hyperkalemia in a subset of patients with underlying renal disease, diabetes mellitus, or those receiving K+-sparing diuretics, ACE inhibitors, or NSAIDs. Pseudohypoaldosteronism is a rare familial disorder characterized byhyperkalemia, metabolic acidosis, renal Na+ wasting, hypotension, high renin and aldosterone levels, and end-organ resistance to aldosterone. ...
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Chapter 046. Sodium and Water (Part 17) Chapter 046. Sodium and Water (Part 17) Decreased aldosterone synthesis may be due to primary adrenalinsufficiency (Addisons disease) or congenital adrenal enzyme deficiency (Chap.336). Heparin (including low-molecular-weight heparin) inhibits production ofaldosterone by the cells of the zona glomerulosa and can lead to severehyperkalemia in a subset of patients with underlying renal disease, diabetesmellitus, or those receiving K+-sparing diuretics, ACE inhibitors, or NSAIDs.Pseudohypoaldosteronism is a rare familial disorder characterized byhyperkalemia, metabolic acidosis, renal Na+ wasting, hypotension, high renin andaldosterone levels, and end-organ resistance to aldosterone. The gene encoding themineralocorticoid receptor is normal in these patients, and the electrolyteabnormalities can be reversed with suprapharmacologic doses of an exogenousmineralocorticoid (e.g., 9α-fludrocortisone) or an inhibitor of 11β-HSDH (e.g.,carbenoxolone). The kaliuretic response to aldosterone is impaired by K+-sparingdiuretics. Spironolactone is a competitive mineralocorticoid antagonist, whereasamiloride and triamterene block the apical Na + channel of the principal cell. Twoother drugs that impair K+ secretion by blocking distal nephron Na+ reabsorptionare trimethoprim and pentamidine. These antimicrobial agents may contribute tothe hyperkalemia often seen in patients infected with HIV who are being treatedfor Pneumocystis carinii pneumonia. Hyperkalemia frequently complicates acute oliguric renal failure due toincreased K+ release from cells (acidosis, catabolism) and decreased excretion.Increased distal flow rate and K+ secretion per nephron compensate for decreasedrenal mass in chronic renal insufficiency. However, these adaptive mechanismseventually fail to maintain K+ balance when the GFR falls below 10–15 mL/min oroliguria ensues. Otherwise asymptomatic urinary tract obstruction is an oftenoverlooked cause of hyperkalemia. Other nephropathies associated with impairedK+ excretion include drug-induced interstitial nephritis, lupus nephritis, sickle celldisease, and diabetic nephropathy. Gordons syndrome is a rare condition characterized by hyperkalemia,metabolic acidosis, and a normal GFR. These patients are usually volume-expanded with suppressed renin and aldosterone levels as well as refractory to thekaliuretic effect of exogenous mineralocorticoids. It has been suggested that thesefindings could all be accounted for by increased distal Cl – reabsorption(electroneutral Na+ reabsorption), also referred to as a Cl–shunt. A similarmechanism may be partially responsible for the hyperkalemia associated withcyclosporine nephrotoxicity. Hyperkalemic distal (type 4)RTA may be due toeither hypoaldosteronism or a Cl– shunt (aldosterone-resistant). Clinical Features Since the resting membrane potential is related to the ratio of the ICF toECF K+ concentration, hyperkalemia partially depolarizes the cell membrane.Prolonged depolarization impairs membrane excitability and is manifest asweakness, which may progress to flaccid paralysis and hypoventilation if therespiratory muscles are involved. Hyperkalemia also inhibits renalammoniagenesis and reabsorption of NH4+ in the TALH. Thus, net acid excretionis impaired and results in metabolic acidosis, which may further exacerbate thehyperkalemia due to K+ movement out of cells. The most serious effect of hyperkalemia is cardiac toxicity, which does notcorrelate well with the plasma K+ concentration. The earliest electrocardiographicchanges include increased T-wave amplitude, or peaked T waves. More severedegrees of hyperkalemia result in a prolonged PR interval and QRS duration,atrioventricular conduction delay, and loss of P waves. Progressive widening ofthe QRS complex and merging with the T wave produces a sine wave pattern. Theterminal event is usually ventricular fibrillation or asystole. Diagnosis (Fig. 46-4) With rare exceptions, chronic hyperkalemia is always due toimpaired K+ excretion. If the etiology is not readily apparent and the patient isasymptomatic, pseudohyperkalemia should be excluded, as described above.Oliguric acute renal failure and severe chronic renal insufficiency should also beruled out. The history should focus on medications that impair K + handling andpotential sources of K+ intake. Evaluation of the ECF compartment, effectivecirculating volume, and urine output are essential components of the physicalexamination. The severity of hyperkalemia is determined by the symptoms,plasma K+ concentration, and electrocardiographic abnormalities. Figure 46-4