Potassium metabolism is one of those things we
just have to know. We can really hurt people if get this one wrong. Here is a
review on the topic. Now, go a eat some bananas !
The plasma potassium level is normally maintained
within narrow limits (typically, 3.5 to 5.0 mmol per liter) by multiple
mechanisms that collectively make up potassium homeostasis. Such strict
regulation is essential for a broad array of vital physiologic processes. The
importance of potassium homeostasis is underscored by the well-recognized
finding that patients with hypokalemia or hyperkalemia have an increased rate
of death from any cause. In addition, derangements of potassium homeostasis
have been associated with pathophysiologic processes, such as progression of
cardiac and kidney disease and interstitial fibrosis.
External
potassium homeostasis regulates renal potassium excretion to balance
potassium intake, minus extrarenal potassium loss and correction for any
potassium deficits. External potassium balance involves three control
systems. Two systems can be categorized as “reactive,” whereas a third system
is considered to be “predictive.” A negative-feedback system reacts to
changes in the plasma potassium level and regulates the potassium balance.
Potassium excretion increases in response to increases in the plasma
potassium level, leading to a decrease in the plasma level. A reactive
feed-forward system that responds to potassium intake in a manner that is
independent of changes in the systemic plasma potassium level has also been
recognized. A predictive system appears to modulate the effect of reactive
systems, enhancing physiologic mechanisms at the time of day when food intake
characteristically occurs — typically, during the day in humans and at night
in nocturnal rodents. This predictive system is driven by a circadian
oscillator in the suprachiasmatic nucleus of the brain and is entrained to
the ambient light–dark cycle. The central oscillator (clock) entrains
intracellular clocks in the kidney that generate the cyclic changes in
excretion. When food intake is evenly distributed over 24 hours, and physical
activity and ambient light are held constant, this system produces a cyclic
variation in potassium excretion.
Internal
potassium homeostasis is the maintenance of an asymmetric distribution of
total body potassium between the intracellular and extracellular fluid
(approximately 98% intracellular and only a small fraction, approximately 2%,
extracellular), which occurs by the balance of active cellular uptake by sodium–potassium
adenosine triphosphatase, an enzyme that pumps sodium out of cells while
pumping potassium into cells (called the sodium–potassium pump rate), and
passive potassium efflux (called the leak rate). Little increase in the
plasma potassium level occurs during potassium absorption from the gut in
normal persons owing to potassium excretion by the kidney and potassium
sequestration by the liver and muscle. Insulin, catecholamines, and
mineralocorticoids stimulate potassium uptake into muscle and other tissues.
Between meals, the plasma potassium level is nearly constant, as potassium
excretion is balanced by the release of sequestered intracellular potassium.
The
healthy kidney has a robust capacity to excrete potassium, and under normal
conditions, most persons can ingest very large quantities of potassium (400
mmol per day or more) without clinically significant hyperkalemia. Potassium
that is filtered at the glomerulus is largely reabsorbed in the proximal
tubule and the loop of Henle. Consequently, the rate of renal potassium
excretion is determined mainly by the difference between potassium secretion
and potassium reabsorption in the cortical distal nephron and collecting
duct. Both of these processes are regulated — potassium ingestion stimulates
potassium secretion and inhibits potassium reabsorption. Factors that
regulate potassium secretion and reabsorption can be divided into those that
serve to preserve potassium balance (homeostatic) and those that affect
potassium excretion without intrinsically acting to preserve potassium
balance (contra-homeostatic). Examples of the latter include flow rate in the
renal tubular lumen and the luminal sodium level. The acid–base balance also
affects potassium excretion. The predominant effect of acidosis is to inhibit
potassium clearance, whereas the predominant effect of alkalosis is to
stimulate potassium clearance.
In
vertebrates, a central clock in the suprachiasmatic nucleus of the brain and
peripheral clocks that are present in virtually all cells regulate circadian
rhythms. Among the many physiologic functions in humans that show circadian
rhythms, few are more consistent and stable than the circadian rhythm of
urinary potassium excretion. The timing signals from the central clock to the
peripheral clocks remain uncertain, but adrenal corticosteroids and agents
from other loci have been proposed or identified. Although the action of
cortisol in promoting potassium excretion would suggest a direct (nonclock)
hormonal effect, studies by Moore-Ede and colleagues indicate that cortisol
serves as a clock synchronizer. Aldosterone also affects certain circadian
clocks and, in particular, acutely induces the expression of period circadian
clock 1 (PER1) in the kidney.
Having a basic understanding of the metabolism of this mineral is important when deciding therapies to treat or prevent potassium plasma level variations. Now you know... be careful when writing for potassium or telling patients to take supplements.
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Thursday, July 23, 2015
Potassium metabolism... enough to make you go Bananas!
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