Hypokalemia – causes, symptoms, diagnosis, treatment, pathology


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much more. Try it free today! 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. And that leaves 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 then reabsorbed at this stage, and it could even 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 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 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. Having said all that, in situations where
somebody produces too much aldosterone, like primary hyperaldosteronism, then there’s
more potassium secretion by the principal cells, meaning more gets excreted, and that
means less potassium is retained, causing 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 means 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, increases 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. Now, 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 already saw, can lead to hypokalemia. Relative to the upper GI tract, the lower
GI tract secretes more potassium, so more gets 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. 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 muscles. 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 contractions of smooth muscles
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 which
leads to respiratory depression. Finally, hypokalemia can affect cardiac muscle
contractions, which can lead to cardiac arrhythmias as well as 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 get 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 an external potassium
balance shift having to do with either low intake or high excretion of potassium. Either way the low potassium levels leads
to issues with muscle contractions, which could be smooth, skeletal, or cardiac muscles.

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