Potassium homeostasis

Definitions & Key takeaways

Potassium homeostasis is the body's ability to maintain a constant balance of potassium in the body. Potassium is a cation mostly located inside the cell and is essential for maintaining the function of excitable tissues. The kidneys play a fundamental role, being responsible for the external potassium balance, particularly the cells of the distal convoluted tubule and collecting duct, which are considered the fine-tuning components of potassium reabsorption and secretion. Kidneys remove excess potassium from the bloodstream and excrete it in the urine.

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Introduction0:00–1:17

Potassium or Kalium is a positive ion, or a cation, noted with a K. About 98% of total body potassium is found in the intracellular fluid, or the ICF for short, which makes for an intracellular potassium concentration of about 150 milliequivalents per liter.
The remaining 2 percent is in the extracellular fluid, or the ECF, which consists of plasma and interstitial fluid. However, since we can only measure the plasma level of potassium, which is about 4.5 milliequivalents per liter, that level is often used to define the normal extracellular concentration of potassium.
Maintaining the normal potassium concentration in the ECF and ICF is essential for the normal functioning of excitable cells like nerve cells and muscle cells, including cardiomyocytes.
Now, across all cell membranes, when there’s no stimulus, there are negative electrical charges on the inside and positive electrical charges on the outside.
This creates a potential difference called the resting membrane potential. Once there’s a stimulus- like when a muscle contracts-, an electrochemical impulse is generated and transmitted along the cell membrane and that generates an action potential.
Okay, now, we get potassium from our diet. The daily recommended potassium intake is about 40 to 50 milliequivalents per liter which is about 1.6 to 2 grams of potassium - which is the equivalent of 5 bananas per day.

Potassium1:17–1:49

Once ingested, potassium is reabsorbed in the blood by the GI tract and travels unbound to plasma proteins. Most of potassium gets inside the cells, a little amount can be lost through sweat and the GI tract and the rest is filtered by the kidneys and excreted.

Potassium Regulation1:49–2:14

Knowing this, potassium needs to be carefully regulated in order for its concentration to remain constant. Potassium balance depends on the total amount of potassium in the body which in turn is determined by potassium intake and excretion and it’s called the external potassium balance.
Potassium balance also depends on the distribution of potassium between the ECF and ICF and is also called the internal potassium balance.
Okay, let’s start with external potassium balance. On a daily basis, the urinary excretion of potassium must be equal to the dietary potassium, minus small amounts of potassium that can be lost through sweat or through the gi tract.

External Potassium Balance2:14–2:48

Now, if potassium excretion is less than potassium intake, then this is a positive potassium balance and hyperkalemia, or increased potassium levels in the blood, can occur.
If potassium excretion is greater than intake, then this is a negative potassium balance and hypokalemia, or low levels of potassium in the blood, can occur.

Nephrons2:48–3:54

So the kidneys have a pretty important job of keeping the potassium balance at a cozy neutral. Now, the kidneys are made up of lots and lots of nephrons, and each nephron is made up of a renal corpuscle and a renal tubule.
The renal corpuscle, in turn, is made up of the glomerulus, which is a tiny clump of capillaries, and Bowman’s capsule surrounding it.
So, blood gets to the glomerulus through the afferent arteriole, which is a branch of the renal artery, and leaves the glomerulus through the efferent arterioles.
These vessels act like a coffee filter, allowing everything but red blood cells and proteins to pass from the bloodstream into Bowman’s capsule - which is connected to the renal tubule.
And the resulting fluid is called filtrate. Now, upon exiting the glomerulus, the efferent arterioles divide into capillaries a second time, forming the peritubular vessels, which wrap around the segments of the renal tubule: the proximal convoluted tubule, the U- shaped loop of Henle, which has a descending and ascending limb, the distal convoluted tubule, and the collecting duct.

Potassium Clearance3:54–5:33

As filtrate passes through the renal tubule, ions like potassium are filtered from the capillaries into the lumen of the tubule, and reabsorbed from the lumen into the capillaries, depending on the amount of potassium in the bloodstream.
First, potassium is freely filtered across glomerular capillaries and moves on in the proximal convoluted tubule or in the PCT where 67 percent of the potassium is reabsorbed.
Interestingly, 67 percent of the water is also reabsorbed in the PCT, leaving the lumen full of all kinds of solutes, like potassium.
As a consequence, some potassium gets dragged passively from the lumen, into the PCT cells and then in the bloodstream. Some of the potassium can also simply get dragged along with water and this is called solvent drag.
Further on, in the thick ascending limb of Henle, an additional 20 percent of the filtered potassium is reabsorbed using the sodium-potassium-chloride cotransporter or NKCC2.
Some medications, like loop diuretics, can block the NKCC2 cotransporter, and this results in increased sodium, chloride, and potassium excretion.
Finally, the distal convoluted tubule and collecting duct are responsible for adjustments in potassium excretion, specifically adjustments when dietary potassium intake varies.
So if a person has a low potassium diet, then more potassium will be reabsorbed in these segments. Conversely, when there’s a normal or a high intake of potassium, more potassium will be secreted by the principal cells of the distal and convoluted tubule into the lumen.

Aldosterone5:33–7:16

This is mostly regulated by aldosterone, a hormone produced in the adrenal glands in response to angiotensin II - which in turn is a part of the renin-angiotensin-aldosterone system that typically responds to low blood pressure.
Aldosterone increases sodium and water reabsorption, to bring blood pressure back up, and this also results in increased potassium secretion.
So first, Aldosterone induces the synthesis of more sodium channels on the apical surface of the distal tubular cells, as well as the collecting duct cells.
This allows for more sodium to enter the cells, so more sodium that can be used for the sodium-potassium ATPase, found on the basolateral surface of the tubular cells.
The sodium-potassium ATPase is a pump that gets two potassium ions inside the cells, and pumps three sodium ions outside the cells.
As a result, sodium is pumped out of the cells and eventually into the bloodstream, while potassium enters the cells. Aldosterone also increases the number of sodium-potassium ATPases and as a result, even more potassium will be pumped into the cell.
In this way, the intracellular potassium concentration increases and this creates a driving force for potassium to be secreted from the cell into the lumen.
Additionally, aldosterone also increases the number of potassium channels in the luminal membrane, so even more potassium gets excreted.
Finally, another regulatory mechanism is the amount of negative ions in the distal tubule or in the collecting duct. When there are more negative ions, like bicarbonate, in the lumen, compared to positive ones, potassium secretion increases to maintain the balance between positive and negative ions.
Okay, let’s switch gears and talk about internal potassium balance - or the distribution of potassium in the ECF versus the ICF.

Internal Potassium Balance7:16–8:08

Internal potassium balance is mainly kept in check by the sodium-potassium ATPases on the surface of all cells. And most factors that regulate the internal potassium balance do that by acting on the sodium-potassium ATP-ase.
So, let’s say an individual eats a huge amount of potassium - like 10, instead of 5 bananas. Well, all that potassium reaches the gi tract and gets reabsorbed in the blood, which could lead to a dangerous rise in the extracellular concentration of potassium.
Fortunately, after eating a meal, a lot of insulin is secreted to help with the uptake of glucose into cells. And insulin also increases the activity of the sodium-potassium ATPase, so more potassium gets inside the cell as well.

Exercise8:08–8:58

Next, catecholamines like epinephrine also increase the activity of the sodium-potassium ATPase, allowing more potassium to enter the cells.
This is particularly important during exercise. On the other hand, during exercise, potassium tends to exit the cells.
That’s because during exercise, we consume a lot of energy that’s normally stored as ATP. Burning ATP for energy opens potassium channels and this way potassium can escape the cells.
In this way, during exercise, there’s a very small increase in extracellular potassium concentration, which helps the skeletal muscle arterioles dilate, allowing more blood flow to the muscles.
But since epinephrine levels also rise a bit during exercise, that limits the amount of potassium that gets out of the cells, maintaining the balance.

Cell Lysis8:58–9:23

Another way for potassium to leave cells is through cell lysis, which is when the cell membranes are damaged and broken down.
This can happen with burns, rhabdomyolysis- which is when the skeletal muscle is damaged- or when cancer cells are destroyed during chemotherapy.
When cell membranes break down, this basically leaves a door open for potassium to get outside the cell, leading to hyperkalemia.

Osmolarity9:23–10:04

Finally, potassium balance is very responsive to changes in serum osmolarity and PH. Osmolarity reflects the number of solute particles per liter of solvent, and normally, the osmolarity of the ICF equals the osmolarity of the ECF, even though the exact composition of solutes differs.
Now, when there’s hyperosmolarity, this means that there’s something in the ECF that creates an osmotic force capable of dragging water from inside the cells - like too many sodium ions.
As water leaves the cells, the intracellular potassium concentration increases and this creates a driving force for potassium to leave the cell, leading to a rise in extracellular potassium.

pH10:04–11:02

On the other hand, PH reflects the concentration of hydrogen ions - and normal blood PH is about 7.4. To maintain PH balance, hydrogen moves in and out of the cells.
In order for hydrogen to move across the cell membrane, it must be accompanied by an anion, meaning a ion with a negative charge, or must be exchanged for another cation, like potassium.
Now, when there’s a primary decrease in the hydrogen concentration in the blood, this is called metabolic alkalosis. As a coping mechanism, hydrogen must leave the cells in exchange for potassium.
More potassium gets inside the cells and this leads to hypokalemia. Alternatively, when there’s a primary increase in the hydrogen concentration in the blood, this is called metabolic acidosis.
As a coping mechanism, hydrogen must enter the cells in exchange for potassium. More potassium leaves the cells and this leads to hyperkalemia.

Review11:02–11:55

Alright, as a quick recap, potassium is a cation that’s mostly located inside the cell and it’s essential for maintaining the function of excitable tissues.
Potassium needs to be carefully regulated in order for its concentration to remain constant. The internal potassium balance is the distribution of potassium across cell membranes.
Insulin, epinephrine increase potassium uptake by cells, exercise, cell lysis and hyperosmolality can increase potassium concentration in the ECF.
Acidosis can increase potassium levels in the ECF, while alkalosis can decrease it. The external potassium balance is represented by the renal mechanisms that maintain potassium in balance and as a general rule, the amount of potassium ingested must be equal to the potassium excreted.
The distal convoluted tubule and collecting duct are responsible for adjustments in potassium excretion.