Hypokalemia

Watch video only
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—potassium in the blood and potassium inside cells, or extracellular and intracellular potassium, respectively.
The extracellular component includes both the intravascular space - 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.
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 potassium ions carry a charge, so the difference in concentration also leads to a difference in charge - establishing an overall electrochemical gradient across the cell membrane.
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 take 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 gets taken 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.
In addition, a small amount dietary potassium is also lost via the sweat and gastrointestinal tract. 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, 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. After a meal and glucose increases in the blood, insulin’s released which binds to cells and stimulates uptake of glucose into cells, and increases the activity of the sodium/potassium pump, which pulls potassium into cells.
People with type I diabetes don’t make enough insulin, and use exogenous 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 special ion transporter that exchanges the hydrogen ion for a potassium ion 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.
But 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.
Now, certain catecholamines can shift potassium movement into cells via the beta-2-adrenergic and alpha-adrenergic receptors on cell membranes.
When activated, beta-2-adrenergic receptors stimulate the sodium-potassium pump, which remember pulls 2 potassium ions in from the blood in exchange for 3 sodium ions.
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.
That said, simply low intake can lead to hypokalemia. like in anorexia, prolonged fasting, or specific types of diets.
Most other causes, though have to do with the kidney’s ability to regulate what stays in the blood and gets excreted into the urine, and the kidney does this by the processes of filtration, reabsorption, and secretion.
First off, potassium is freely filtered into the urine at the glomerulus. After that, about 67% or ⅔ is reabsorbed in the proximal convoluted tubule, and an additional 20% is reabsorbed in the thick ascending limb.
That leaves 13% of the initial amount, and at this point the distal tubule and collecting ducts of the nephron can either reabsorb or secrete potassium depending on what the body needs.
Reabsorption in this area is taken care of by the alpha-intercalated cells, while secretion is controlled by the principal cells.
Typically for people on a normal diet, more potassium is secreted then reabsorbed at this stage, and it could be that all of the remaining potassium is secreted out if it’s simply not needed.
An important hormone that helps regulate potassium reabsorption or secretion in the kidneys is aldosterone. Aldosterone increases sodium channels on the lumen side of the principal cell and and sodium-potassium pumps on the basolateral side of the principal cells.
This allows sodium to move from the tubule into the cell, and then to get pumped into the blood by the sodium-potassium pumps.
As the pumps collectively move more sodium into the blood under the influence of aldosterone, more potassium gets pumped into the cell - thereby raising the intracellular potassium concentration.
Aldosterone also increases the number of potassium channels on the lumen side of the principal cells, so having more intracellular potassium and also having more potassium channels promotes potassium secretion.
All that being said, in situations where somebody produces too much aldosterone, like primary hyperaldosteronism, then there’s more potassium secretion by the principal cells and excreted, and therefore less potassium is retained, leading to hypokalemia.
Other pathological conditions that cause increased aldosterone levels include compensated heart failure and cirrhosis. Commonly used diuretics, like loop diuretics and thiazide diuretics, also increase potassium excretion and can lead to hypokalemia.
These diuretics inhibit sodium reabsorption upstream of the principal cells, which meanis more sodium is delivered downstream to the principal cells.
As a result, more sodium enters the principal cells and is available for the sodium-potassium pump, which pumps sodium out into the blood and pumps potassium into the cell, creating a relatively high potassium concentration in the principal cell.
In addition, these diuretics also allow more water to remain in the lumen, creating a relatively low potassium concentration in the lumen.
Taken together, a relatively high potassium concentration in the principal cell and a relatively low potassium concentration in the lumen, strengthens the potassium gradient and causes a lot of potassium to get secreted and excreted in the urine - leading to hypokalemia.
Another external balance shift causing hypokalemia is increased losses of gastrointestinal secretions, typically due to vomiting and diarrhea.
The upper GI tract actually only secretes a small amount of potassium, so direct losses via vomiting are usually minimal.
But the loss of stomach acid leads to metabolic alkalosis, which as we saw, can lead to hypokalemia. Relative to the upper GI tract, the lower GI tract secretes more potassium, so more is directly lost in the feces in cases of chronic diarrhea, like from infections, inflammatory bowel diseases, as well as laxative abuse.
Finally, a very small amount of potassium is also lost in sweat, which could be relevant for individuals who exercise a lot in a hot climate or enjoy eating spicy foods!
Alright, so there are all these ways to develop hypokalemia, but what happens when somebody has hypokalemia? Well remember that the concentrations of potassium inside and outside of cells is really—super—important for maintaining the resting cell membrane potential, and ultimately for allowing a cell to depolarize and a muscle to contract, and that includes all muscles—skeletal, smooth, and cardiac.
So, with low potassium in the blood, the membrane potential can hyperpolarize, or become more negative. This means that these muscle cells become less reactive to stimuli.
Diminished smooth muscle contraction in the bowels can lead to constipation. Diminished skeletal muscle contractions can lead to muscle weakness, cramps, and flaccid paralysis, which tends to begins in the lower extremities and ascends upward.
Respiratory muscles may also be affected leading to respiratory depression. Finally, hypokalemia can affect cardiac muscle contractions, which can lead to cardiac arrhythmias and cardiac arrest.
Hypokalemia is diagnosed based on the presence of an low levels of potassium in the blood, generally below 3.5 mEq/L. It’s also important to obtain an electrocardiogram, which typically shows a prolonged QT interval, appearance of a U wave, and atrial or ventricular tachyarrhythmias.
In patients with severe hypokalemia, the main goal of treatment is to normalize potassium levels. This is done by reducing ongoing potassium losses by treating underlying causes like vomiting and diarrhea and using potassium-sparing diuretics if diuretic therapy is required, as well as replenishing potassium stores with supplementation.
Alright, as a quick recap, hypokalemia describes a low concentration of potassium in the blood, which can be the result of internal potassium balance shift where potassium moves into the body’s cells, as well as external potassium balance shift having to do with either low intake or high excretion of potassium.
Low potassium levels leads to issues with muscle contractions, which could be smooth, skeletal, or cardiac muscles. Thanks for watching, you can help support us by donating on patreon, or subscribing to our channel, or telling your friends about us on social media.