Hyperkalemia

With hyperkalemia, hyper- means over and -kal- refers to potassium, and -emia refers to the blood, so hyperkalemia means higher than normal potassium levels in the blood, generally over 5.5 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.

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 sweat.So, in order for there to be too much potassium in the blood, or hyperkalemia, there are two possibilities.The first is an external balance shift, which is most often caused by a decrease in sodium excretion in the kidneys, which raises the level of potassium in the blood.The second is an internal balance shift where potassium moves out of cells, and into the interstitium and blood.

One potential cause of an internal potassium balance shift is insulin deficiency.This is because, after a meal, glucose increases in the blood, and at the same time, insulin gets released which binds to cells and stimulates 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, so when they eat a meal—especially a meal with a lot of potassium—that potassium sits in the blood instead of being taken into cells, and this causes hyperkalemia.Another cause of an internal potassium balance shift could be an acidosis, which is when the blood becomes too acidic, in other words, there’s a higher concentration of hydrogen ions—which means a lower blood pH.One way the body can increase the blood pH is by moving hydrogen ions out of the blood and into cells.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 acidosis, hydrogen ions enter cells and potassium ions leave the cells and enter the blood, which might help with the acidosis, but results in hyperkalemia.Now, this isn’t always the case for acidosis, though.

in respiratory acidosis, potassium levels aren’t affected because CO2 is lipid soluble and freely moves into cells without being exchanged for potassium, therefore no hyperkalemia.Similarly, when there’s a metabolic acidosis from excess organic acids like lactic acid and ketoacids, protons can enter cells with the organic anion rather than having to get exchanged for potassium ions.Certain catecholamines can also shift potassium out of cells, and this is via 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 antagonists, also known as beta blockers, and alpha-adrenergic agonists, both cause a shift in potassium out of the cells and into the blood.Another important mechanism is hyperosmolarity, which is where there is an increased extracellular osmolarity, relative to the intracellular space.

This osmotic gradient pulls water out of cells and into the extracellular space.Less water in the cells increases the intracellular potassium concentration, which increases potassium’s concentration gradient, and pushes more of it out of the cell and into the interstitium and blood.

Cell lysis is yet another cause of hyperkalemia.Since so much potassium is kept within the cell, when a large number of cells die or lyse, potassium is released into the blood, which causes hyperkalemia.Examples of large-scale cell lysis are severe burns, rhabdomyolysis or breakdown of skeletal muscle, and tumor lysis as a result of chemotherapy.

A final example of internal potassium balance leading to hyperkalemia is exercise.During exercise while the body and the body’s cells are working harder, more cellular ATP, which is the molecular unit of currency—gets consumed.The depletion of ATP triggers potassium channels on the membrane of muscle cells to open up, which allows potassium to moves down its electrochemical gradient and out of the cell.Usually this shift is small, but if combined with beta-blockers or kidney issues, strenuous exercise can lead to hyperkalemia.Alright, on to external potassium balance shifts resulting in hyperkalemia, which has to do with potassium intake and excretion.That said, simply taking in too much potassium can lead to hyperkalemia, but this would typically from rapid, excessive infusion of potassium into the bloodstream, like in patients receiving intravenous fluids, and this would be considered an iatrogenic cause, which means that it results from a medical treatment or procedure.Most other cases, though have to do with the kidney’s, and their 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, and that leaves about 13% of the initial amount, right?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.Now, 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 than reabsorbed at this stage, and it could be that all of the remaining potassium is secreted out if it’s simply not needed.Now, an important hormone that helps regulate potassium reabsorption or secretion in the kidneys is aldosterone.Aldosterone increases the number of sodium channels and the number of potassium channels on the lumen side of the principal cell as well as 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, which raises the intracellular potassium concentration.Having more intracellular potassium and also having more potassium channels promotes potassium secretion.All that being said, in situations where somebody’s unable to produce enough aldosterone, or hypoaldosteronism or adrenal insufficiency, then there’s less potassium secretion by the principal cells, and therefore more potassium is retained, leading to hyperkalemia.Along the same lines, drugs that reduce the effect of aldosterone can also cause hyperkalemia, and these are drugs like renin inhibitors, ACE inhibitors, angiotensin II receptor antagonists, selective aldosterone blockers, and potassium-sparing diuretics.Now, acute kidney injury can cause a low glomerular filtration rate, which is the volume of blood filtered through the kidney over a period of time, and this can lead to oliguria and hyperkalemia.In these situations, the nephron tries to hold on to salt and water, so by the time filtrate has moved into the distal tubule, there’s very little of both sodium and water remaining in the lumen.

Having little water in the lumen, creates a relatively high potassium concentration in the lumen.In addition to this, because less sodium is in the distal tubule, less of it moves through the luminal sodium channel into the principal cell and gets pumped over to the other side by the basolateral sodium-potassium pump.And this means less potassium gets into the principal cell, creating a relatively low potassium concentration in the principal cell.And this leads to more potassium in the blood and hyperkalemia.

Alright, so there are all these ways to develop hyperkalemia, but what happens when somebody has hyperkalemia?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 too much potassium outside the cell, the membrane potential can become more positive, to the point of even causing contraction.

Initially this might cause mild intestinal cramping.But eventually, the resting membrane potential gets so high that it’s above the threshold potential, meaning that once the muscle depolarizes and contracts, it can’t repolarize to allow another contraction.In skeletal muscles, this can cause weakness and flaccid paralysis, that starts in the lower extremities and ascends upward.Hyperkalemia, though, also affects cardiac muscle contractions, which can lead to cardiac arrhythmias and cardiac arrest.

Hyperkalemia is diagnosed based on the presence of an elevated potassium levels in the blood, generally over 5.5 mEq/L.It’s also important to get an electrocardiogram, which typically shows tall, peaked T waves with a narrow base best seen in the precordial leads V1 through V6, as well as a shortened QT interval, and ST-segment depression.In severe cases, it can also cause a prolonged PR interval, a diminished or absent P wave, and a widened QRS complex.With severe hyperkalemia, treatment might be done by using calcium to stabilize the myocardial cell membrane, using insulin, glucose, beta-adrenergic agonists, and sodium bicarbonate to shift potassium into the intracellular space, using resins that bind potassium to promote potassium elimination in the gastrointestinal tract, using potassium-wasting diuretics to promote potassium elimination in the kidneys, and in severe cases—dialysis.Alright, as a quick recap, hyperkalemia describes a high concentration of potassium in the blood, which can be the result of shifts in internal potassium balance where potassium moves out of the body’s cells, as well as external potassium balance problems having to do with the intake of potassium and typically the kidney’s ability to to regulate its excretion.

Either way, the high potassium levels leads to muscle problems, which could be smooth, skeletal, or cardiac muscles. Agonist and sodium bicarbonate to shift, potassium into the intracellular space using resin that bind potassium to promote potassium elimination.

In the gastrointestinal tract, using potassium, wasting diuretics to promote, potassium elimination, the kidneys and severe cases, dialysis.

All right, as a quick recap, hyperkalemia describes a high concentration of potassium in the blood, which can be the result of shifts in internal potassium.

Balance were potassium moves out of the body cells as well as external potassium balance problems, having to do with the intake of potassium in typically the kidneys ability to regulate its excretion.

Either way, the high potassium leads to issues with muscle contractions, which could be issues with the smooth skeletal or