With hypokalemia, hypo- means under and -kal- refers to potassium, and -emia refers to the blood, so hypokalemia means lower than normal potassium levels in the blood, generally under 3.5 mEq/L.

Now, total body potassium can essentially be split into two components—intracellular and extracellular potassium, or potassium inside and outside cells, respectively.

The extracellular component includes both the intravascular space, which is the space within the blood and lymphatic vessels and the interstitial space—the space between cells where you typically find fibrous proteins and long chains of carbohydrates which are called glycosaminoglycans.

Now, the vast majority, around 98%, of all of the body’s potassium is intracellular, or inside of the cells.

In fact, the concentration of potassium inside the cells is about 150 mEq/L whereas outside the cells it’s only about 4.5 mEq/L.

Keep in mind that these potassium ions carry a charge, so the difference in concentration also leads to a difference in charge, which establishes an overall electrochemical gradient across the cell membrane.

And this is called the internal potassium balance. This balance is maintained by the sodium-potassium pump, which pumps 2 potassium ions in for every 3 sodium ions out, as well as potassium leak channels and inward rectifier channels that are scattered throughout the membrane.

This concentration gradient is extremely important for setting the resting membrane potential of excitable cell membranes, which is needed for normal contraction of smooth, cardiac, and skeletal muscle.

Also, though, in addition to this internal potassium balance, there’s also an external potassium balance, which refers to the potassium you get externally through the diet every day.

On a daily basis the amount of potassium that typically gets taken in, usually ranges between 50 mEq/L to 150 mEq/L, which is way higher than the extracellular potassium concentration of 4.5 mEq/L, so your body has to figure out a way to excrete most of what it takes in.

This external balancing act is largely taken care of by the kidneys, where excess potassium is secreted into a renal tubule and excreted in the urine.

Also, though, a small amount dietary potassium is also lost via the gastrointestinal tract and the sweat.

So, in order for there to be too little potassium in the blood, or hypokalemia, there are two possibilities, the first is an external balance shift most often caused by an increase in potassium excretion in the kidneys, which lowers the level of potassium in the blood, and the second is an internal balance shift where potassium moves into of cells, from the interstitium and blood.

One potential cause of an internal potassium balance shift is having excess insulin.

This is because, after a meal, glucose increases in the blood, and at the same time insulin’s released, which binds to cells and stimulates the uptake of that glucose.

Insulin also increases the activity of the sodium/potassium pump, which pulls potassium into cells.

People with type I diabetes don’t make enough insulin, and so they use exogenous insulin, meaning an injection or infusion of insulin.

In rare cases, insulin overdose can cause enough potassium uptake into cells as to cause hypokalemia.

Another cause of an internal potassium balance shift could be an alkalosis, which is when the blood becomes too alkaline, in other words, there’s a lower concentration of hydrogen ions—meaning a higher blood pH.

One way the body can decrease blood pH is by moving hydrogen ions out of cells and into the blood.

To accomplish this, cells use a complex series of multiple ion channels, exchangers, and pumps to exchange hydrogen ions for potassium ions across the cell membrane.

So in order to help compensate for an alkalosis, hydrogen ions leave cells and potassium ions enter the cells and leave the blood, resulting in hypokalemia.

That being said, not all acid-base disturbances affect potassium levels.

For example, in respiratory alkalosis due to low carbon dioxide levels in the blood, potassium levels aren’t typically affected because CO2 is lipid soluble and freely moves into or out of cells without being exchanged for potassium, therefore no hypokalemia.

Certain catecholamines can also shift potassium movement into cells, and this is via the beta-2-adrenergic and alpha-adrenergic receptors on cell membranes.

When activated, beta-2-adrenergic receptors stimulate the sodium-potassium pump, which pulls potassium from the blood into cells.

Meanwhile alpha-adrenergic receptors cause a shift of potassium out of cells via calcium-dependent potassium channels.

So, that said, beta-2-adrenergic agonists and alpha-adrenergic antagonists, both cause a shift in potassium into cells and out of the blood.

Alright, on to external potassium balance shifts resulting in hypokalemia, which has to do with potassium intake or excretion.

With regards to intake, simply not taking enough potassium in can lead to hypokalemia, like in the case of anorexia, prolonged fasting, or specific types of diets.

Most other cases, though, have to do with the kidney’s ability to regulate what stays in the blood and gets excreted into the urine.

The kidney does this by the processes of filtration, reabsorption, and secretion in the nephron.

First off, potassium is freely filtered from the blood into the urine at the glomerulus.

After that, about 67% is reabsorbed in the proximal convoluted tubule, and an additional 20% is reabsorbed in the thick ascending limb.

Video - Hypokalemia

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