Chapter 046. Sodium and Water (Part 17) ppt

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 NH
4
+
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