Describe potassium homeostasis in the body and its functional

importance
Introduction
Potassium homeostasis has functional importance for membrane potential, particularly relevant in
the heart and respiratory muscles, and is important for several other functions in the body. There
are 2 moles of potassium in intracellular fluid whereas the value for extracellular fluid is measured in
millimoles; resultantly, the body’s main control of potassium homeostasis in the short term is to
facilitate potassium transfer into cells. Secondarily, there is also slower renal control of potassium
homeostasis, both regulated and unregulated, in long-term control of potassium homeostasis.

Functional importance of potassium homeostasis

Potassium is the major intracellular organ in the body and as such is the major determinant of
resting membrane potential (the Nernst potential of potassium is -90mV); resultantly hyperkalaemia
and hypokalaemia both are major stresses on normal function of the body, as they modulate the
excitability of cells such as skeletal and cardiac muscle, resulting in tetany/muscle weakness and
cardiac arrhythmia respectively. Effects on the diaphragm such as paralysis may lethally impair
respiration. Also, potassium is required for the fixed stoichiometry of the Na+/K+ ATPase (sodium
pump), cell volume control and transmembrane transport. Eating is a major stress to potassium
homeostasis due to its sporadic nature, while exercise is a major stress because a high rate of action
potentials (perhaps reaching tetany) in skeletal muscle where 70% of body potassium is stored can
significantly increase extracellular potassium.

Extracellular to intracellular potassium shift

During anticipation of eating, the body releases insulin through feedforward control from the beta
cells in the islets of the Langerhans in the pancreas, which promotes potassium entry into cells
through upregulation of the sodium pump as well as increasing glucose entry into muscle and fat
cells through GLUT4 channels. In unmanaged or poorly managed type 1 diabetes, lack of insulin
release due to autoimmune destruction of insulin-producing cells may predispose patients to
hyperkalaemia. Meanwhile, there is also feedforward control during exercise through the release of
adrenaline, which also upregulates the sodium pump through its action on beta-1 adrenergic
receptors. Finally, aldosterone release is through the pathway of angiotensinogen (inactive
precursor) conversion to partially active angiotensin 1 by renin secretion by the afferent arteriole
conversion to active angiotensin 2 by ACE (mostly found in the capillary bed of the lungs, as the
whole cardiac output passes through this); aldosterone also upregulates the sodium pump, but also
has effects on the kidney which will be discussed below.

Unregulated renal control of potassium

70% of potassium reabsorption in the kidney occurs in the proximal convoluted tubule regardless of
blood plasma potassium concentration; a further 20% is reabsorbed in the loop of Henle. Potassium
movement out of the filtrate in the PCT and descending LoH is mostly paracellular and follows water,
whereas in the thick ascending limb of the LoH and DCT (where control is mostly regulated),
movement is mostly transcellular. In the thick ascending LoH, the majority of transcellular transport
is through NKCC2 channels. Meanwhile, DCT transport is mainly through the K+/H+ cotransporter
ATPase, which is affected by pH, and so when acidity is increased there is greater potassium
reabsorption.

Regulated renal control of potassium

There is intrinsic regulation in that the increased potassium concentration increases activity of the
sodium pump, increasing secretion. Aldosterone secretion by the zona glomerulosa (which also
releases other mineralocorticoids) of the adrenal cortex causes expression of transcription factors
which increase the number of ENaC channels, which bring more sodium into the cell, increasing
activity of the sodium pump. It also upregulates the SK channels which are calcium activated and
there is evidence that aldosterone also increases density of the sodium pump on the basolateral
membrane. During hypervolaemia, greater glomerular filtration rate causes high tubular flow rates;
as this reduces the extent of equilibration between tubular fluid and extra cellular fluid as there is
less time for exchange, it enhances secretion. Finally, antidiuretic hormone (ADH) produced in the
hypothalamus and released by the neurohypophysis to increase water reabsorption would be
expected to reduce K+ excretion as it reduces tubular flow rate, but this effect is not observed as
ADH also upregulated SK channels.

Clinical stresses on potassium homeostasis

Hyperkalaemia can be induced by renal failure when the kidneys are working below 20% of normal
levels as there is insufficient calcium secretion. Also, as intracellular fluid is the body’s major K+
store, cell lysis, for example as a result of burns or tumour treatment, can release large quantities of
K+ into the ECF. Interestingly, a blood sample may indicate ‘pseudohyperkalaemia’ if done poorly, as
cell lysis has occurred in the process. Hypokalaemia may be induced by reduced food consumption,
for example when a patient is ‘nil by mouth’, or through diarrhoea and vomiting. Diuretics, which
increase tubular flow rate, can also be a factor as they may increase K+ secretion excessively through
increased tubular flow rate.

Conclusion
Potassium homeostasis in the body is vital to life and faces major stresses in daily life, of which
eating and exercise have been discussed. The balance of intake against insensible losses such as
sweating is regulated by the kidneys; however, during hyperkalaemia and hypokalaemia the short-
term major action of homeostasis is the extracellular to intracellular potassium shift through the
actions of insulin and adrenaline as feedforward control and aldosterone as negative feedback. In
the longer term, both unregulated and regulated reabsorption by the kidney have been discussed,
especially the role of the latter in restoring potassium levels in the body to normal.