Chapter 046. Sodium and Water (Part 17) ppt

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 un

Chapter 046 Sodium and Water

(Part 17)

Decreased aldosterone synthesis may be due to primary adrenal

insufficiency (Addison's 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 by

hyperkalemia, metabolic acidosis, renal Na+ wasting, hypotension, high renin and aldosterone levels, and end-organ resistance to aldosterone The gene encoding the mineralocorticoid receptor is normal in these patients, and the electrolyte abnormalities can be reversed with suprapharmacologic doses of an exogenous mineralocorticoid (e.g., 9α-fludrocortisone) or an inhibitor of 11β-HSDH (e.g., carbenoxolone) The kaliuretic response to aldosterone is impaired by K+-sparing

diuretics Spironolactone is a competitive mineralocorticoid antagonist, whereas amiloride and triamterene block the apical Na+ channel of the principal cell Two other drugs that impair K+ secretion by blocking distal nephron Na+ reabsorption are trimethoprim and pentamidine These antimicrobial agents may contribute to the hyperkalemia often seen in patients infected with HIV who are being treated

for Pneumocystis carinii pneumonia

Hyperkalemia frequently complicates acute oliguric renal failure due to increased K+ release from cells (acidosis, catabolism) and decreased excretion Increased distal flow rate and K+ secretion per nephron compensate for decreased renal mass in chronic renal insufficiency However, these adaptive mechanisms eventually fail to maintain K+ balance when the GFR falls below 10–15 mL/min or oliguria ensues Otherwise asymptomatic urinary tract obstruction is an often overlooked cause of hyperkalemia Other nephropathies associated with impaired

K+ excretion include drug-induced interstitial nephritis, lupus nephritis, sickle cell disease, and diabetic nephropathy

Gordon's 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 the kaliuretic effect of exogenous mineralocorticoids It has been suggested that these findings could all be accounted for by increased distal Cl– reabsorption (electroneutral Na+ reabsorption), also referred to as a Cl–shunt A similar

mechanism may be partially responsible for the hyperkalemia associated with

cyclosporine nephrotoxicity Hyperkalemic distal (type 4)RTA may be due to

either hypoaldosteronism or a Cl– shunt (aldosterone-resistant)

Clinical Features

Since the resting membrane potential is related to the ratio of the ICF to ECF K+ concentration, hyperkalemia partially depolarizes the cell membrane Prolonged depolarization impairs membrane excitability and is manifest as weakness, which may progress to flaccid paralysis and hypoventilation if the respiratory muscles are involved Hyperkalemia also inhibits renal ammoniagenesis and reabsorption of NH4+ in the TALH Thus, net acid excretion

is impaired and results in metabolic acidosis, which may further exacerbate the hyperkalemia due to K+ movement out of cells

The most serious effect of hyperkalemia is cardiac toxicity, which does not correlate well with the plasma K+ concentration The earliest electrocardiographic changes include increased T-wave amplitude, or peaked T waves More severe degrees of hyperkalemia result in a prolonged PR interval and QRS duration, atrioventricular conduction delay, and loss of P waves Progressive widening of the QRS complex and merging with the T wave produces a sine wave pattern The terminal event is usually ventricular fibrillation or asystole

Diagnosis

(Fig 46-4) With rare exceptions, chronic hyperkalemia is always due to impaired K+ excretion If the etiology is not readily apparent and the patient is asymptomatic, pseudohyperkalemia should be excluded, as described above Oliguric acute renal failure and severe chronic renal insufficiency should also be ruled out The history should focus on medications that impair K+ handling and potential sources of K+ intake Evaluation of the ECF compartment, effective circulating volume, and urine output are essential components of the physical examination The severity of hyperkalemia is determined by the symptoms, plasma K+ concentration, and electrocardiographic abnormalities

Figure 46-4