POTASSIUM METABOLISM
Saturday, April 09, 2005
 
Potassium is influenced by factors such as insulin and epinephrine, which increase cellular uptake
This article has been published by the International Biopharmaceutical Association www.ibpassociation.org . Please note this article does not give any medical advice.

The project is sponsored by Kriger Research - CRO and Training Services ( www.kriger.com ) and ClinQua CRO (www.clinqua.com )

Start your Clinical Research Career Now


1. Intracellular fluid has about 3000 mEq of potassium; extracellular fluid only 65 mEq. This ratio must be maintained in order to enable the proper functioning of cell membranes.
2. Potassium is influenced by factors such as insulin and epinephrine, which increase cellular uptake, and high total body potassium levels, which reduce cellular uptake.
3. Within the kidney, aldosterone stimulates the secretion of potassium and the reabsorption of sodium. Diuretics cause increased potassium secretion due to increased sodium and fluid in the collecting tubules.



HYPOKALEMIA

Definition:
1. Serum potassium under 3.5 mEq/L
2. Most potassium is intracellular and so it takes severe depletion of intracellular potassium before any changes in serum potassium are felt.
Etiology:
1. Renal causes
a. Primary hyperaldosteronism as in adrenal tumors, adrenal hyperplasia or ectopic ACTH can cause hypokalemia. Excess ingestion of European licorice or some tobacco products also causes hypokalemia via primary hyperaldosteronism.
b. Tumors, renal artery stenosis or malignant hypertension may cause secondary hyperaldosteronism. It is also the mechanism for the hypokalemia seen in congestive heart failure and cirrhosis.
c. Potassium wasting is seen in renal tubular acidosis types I (distal) and II (proximal). High levels of renin and aldosterone, renal potassium wasting, metabolic acidosis and polyuria characterize Bartter’s syndrome. Chronic magnesium depletion causes potassium wasting which is refractory to potassium supplements and needs magnesium supplementation first.
d. Drugs such as diuretics, penicillins, gentamicin, and amphotericin B increase potassium excretion.
2. Extrarenal causes
a. Low intake or gastrointestinal losses from diarrhea and/or vomiting, chronic laxative use
b. Redistribution of potassium from plasma to intracellular fluid – as with insulin, adrenaline, bicarbonate.
c. Therapies for megaloblastic anemia (and neoplasms) deplete potassium stores due to cell proliferation.
d. Hypokalemic periodic paralysis is a rare syndrome with rapid drops in potassium levels and resultant paralysis.

Manifestations:
1. Muscle weakness and paralysis
2. Abnormalities of insulin secretion and increased glucose intolerance, polyuria
3. Arrythmias (especially with digitalis intoxication)
Diagnosis:
1 Potassium less than 20 mEq/L in urine suggests extrarenal losses; more than 30 mEq/L is characteristic of renal losses.
2 If the patient also suffers from hypertension, excess mineralocorticoid activity or the use of diuretics should be suspected as a cause of the hypokalemia. If blood pressure is normal, the cause is more likely to be either primary renal or due to gastrointestinal losses.
3 Acidosis and hypokalemia are found in renal tubular acidosis.
Invasive tests may be needed to establish a diagnosis of primary aldosteronism or to see if adrenal disease is uni- or bilateral. In these cases, blood levels of aldosterone, renin and cortisol are measured at the renal veins.
4 Non-invasive tests such as the renin stimulation test (which distinguishes between renin over-secretion and primary adrenal disease) and the aldosterone suppression test (which diagnoses primary hyperaldosteronism) may aid in diagnosis.
a. The renin test consists of measuring plasma renin in the morning with the patient lying down, administering 80 mg of furosemide, and then measuring renin again after 3 hours of standing. The normal reaction is increased renin after furosemide, and the levels should rise even more after standing up. People with hyperaldosteronism will show no increase after furosemide or when standing up. About 20% of patients with essential hypertension will show the same results, even without hyperaldosteronism.
b. The aldosterone test consists of measuring aldosterone in subjects lying down and standing up after infusing 1-2 liters of normal saline. Normal results show suppression of aldosterone levels; patients with primary aldosterone overproduction will not show this suppression.

Principles of management:
1. Potassium supplementation, intravenous or oral, is the first line of therapy. Rate of intravenous administration should be less than 60 mEq/hr and concentration of the solution less than 60 mEq/L. The object is to slowly restore potassium levels to normal. The patient’s heart should be monitored until the potassium levels are normal.
2. Patients receiving diuretics other than potassium sparing diuretics should receive oral potassium supplements and have serum potassium levels tested regularly.


HYPERKALEMIA
Definition:
Serum potassium levels more than 5.5 mEq/L

Etiology:
1. Renal causes
a. Aldosterone deficiency may be due to decreased renin production in renal disease, primary adrenal disease or congenital enzyme defects. Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce renin secretion.
b. Severe renal failure with GFR less than 10 ml/min causes disturbances in potassium transport in the tubules.
c. Aldosterone resistance is seen in renal disease due to sickle cell anemia, SLE, amyloidosis, interstitial renal disease, and obstructive nephropathy and in the use of potassium-sparing diuretics or spironolactone.
2. Extrarenal causes – lack of insulin, succinylcholine use, acute cell necrosis, crush injury, hemolysis, acidosis, hyperosmolarity and hyperkalemic periodic paralysis (rarer than the hypokalemic form) all cause hyperkalemia.
3. Pseudohyperkalemia may occur after blood is drawn due to hemolysis. The actual potassium level may be normal, but hemolysis causes it to be artificially high. In this case, blood should be drawn again and processed quickly.

Manifestations:
1 Weakness or paralysis due to changes in transmembrane potential.
2 Changes in EKG tracings such as longer PR intervals, peaked T waves, longer QRS intervals occur at the beginning and as levels rise, ventricular tachycardia, ventricular fibrillation and asystole may be seen. Arrythmias usually appear at levels above 6 mEq/L.

Diagnosis:
1 Rule out pseudohyperkalemia by measuring both serum and plasma concentrations or by repeating the blood test.
2 Values of more than 50mEq/L urinary potassium are associated with increased intake or cell lysis. Less than 30 mEq/L is seen with renal causes.
3 Blood levels of renin and or aldosterone may be necessary to pinpoint etiology.

Principles of management:
1. Acute therapy consists of redistributing the potassium to protect cardiac function. This can be achieved by administering calcium chloride, sodium bicarbonate, beta-adrenergic agonists or glucose plus insulin.
2. Removal is achieved by the use of loop diuretics, aldosterone, cation-exchange resins (Kayexalate) or, if necessary, dialysis.



For more information on Clinical Research Career Training and Clinical Trials Services please contact Kriger Research Group ( www.kriger.com ) at info@kriger.com or call (866) 757-9791 (USA and Canada) or + 1(416) 630-0038 (Internationally)

Powered by Blogger