Renal Chapter 8: Renal Regulation of Potassium Balance Flashcards Preview

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Flashcards in Renal Chapter 8: Renal Regulation of Potassium Balance Deck (40)
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Describe the intracellular vs extracellular distribution of K.

What is the normal extracellular value?

vast majority is intracellular, only about 2% of total body potassium is extracellular

(that ECF component is highly regulated and crucial for body function)

normal ECF value of K is between 3-5mEq/L (4mEq/L -book)


What effect will raising or lowering extracellular K concentration have?

depolarizes the resting membrane potential, perturbing cell excitability

lowering extracellular potassium usually hyperpolarizes cell membranes


What is extracellular potassium concentration dependent on?

total amount of K in body

distribution of potassium between ECF and ICF compartments

total body K is balance between K intake and excretion
(normal people remain in K balance, as they do in Na balance, by excreting an amount of urinary K equal to the amount ingested minus small amounts eliminated in feces and sweat


What tissue contributes most to sequestration of K? (On a moment-to-moment basis, what protects ECF from large swings in K conc.?)

skeletal muscle bc it contains the largest collection of intracellular volume

muscle effectively buffers extracellular potassium by taking up or releasing it and keeping the plasma potassium conc. close to normal.


What hormones/factors cause K uptake by muscle?

insulin and epi

stimulate plasma membrane Na/K-ATPase


When a large increase in plasma K concentration occurs, what role does insulin play?

a large increase in plasma potassium concentration
facilitates insulin secretion at any time, and the additional insulin induces
greater potassium uptake by the cells, a negative feedback system for opposing
acute elevations in plasma potassium concentration

insulin also stimulates glucose uptake and metabolism by cells (a necessary source of energy to drive the insulin-activated Na-K-ATPase responsible for moving K into cells)


Describe the effect of epi on cellular potassium uptake. When is this most important?

exercise and trauma

in exercise, K moves out of muscle cells that are rapidly firing action potentials and damaged cells leak K
(both cases this raises extracellular K conc.)

exercise or trauma also increase adrenal secretion of epi and epi stimulates K uptake by other cells which partially offsets the outflow from exercising or damaged cells.


How does an increase in ECF hydrogen ion concentration (acidosis) affect K movement in/out of cells?

increase in ECF H ion conc. is associated w net K movement out of cells

decrease in ECF H ion conc. causes net K movement into cells


Will inhibition or activation of Na-K-ATPase cause acidosis or alkalosis?

inhibition of pump- acidosis

activation of pump-alkalosis


Describe how K is handled by kidney.

Where is the chief means of regulation in the nephron for K secretion?

Potassium is freely filtered into Bowman’s space. Under all conditions almost
all the filtered load (~90%) is reabsorbed by the proximal tubule and thick
ascending limb of the loop of Henle. Then, if the body is trying to conserve potassium,
most of the rest is reabsorbed in the distal nephron and medullary collecting
duct, leaving almost none in the urine. In contrast, if the body is ridding itself of potassium, a large amount is secreted in the distal nephron, resulting in a large excretion. When secretion occurs at high rates, the amount excreted may exceed
the filtered load.
(DISTAL segments where most regulation of K excretion is exerted)

The chief means of regulation lies in control over secretion in
parts of the nephron beyond the loop of Henle


Where is most K reabsorbed? How?

What drives this reabsorption?

(Describe all segments of nephron where K reabsorption takes place, describe how.

65% filtered load reabsorbed in proximal tubule, mostly by paracellular route

Some of the flux is driven by the concentration gradient set up
when water is reabsorbed (thus concentrating all solutes remaining in the tubular
lumen). Some may also move by entrainment with the rapidly reabsorbed water
(solvent drag)

also TAL by Na-K-2Cl multiporter in luminal membrane which reabsorbs K.
some of this K is returned to lumen across apical membrane via K channels and rest exits cells across the BL membrane by combination of passive flux through channels and through symporters with Cl (net transcellular reabs.)

Usually about 25% of the filtered load is reabsorbed in the thick ascending
limb, so that only about 10% is passed on to the distal nephron.
medullary collecting duct reabs. too (has little overall effect)

Table 8-1 p 152


Describe how the active transport of K is coupled to other ions.

active influx of K across BL membrane (Na/K ATPase) coupled w efflux of sodium

influx of K across luminal membranes via H-K antiporters accompanied by efflux of protons

potassium is being put into the interstitium surrounding the proximal tubule, this pumped potassium must therefore recycle
right back to the interstitium by passive flux through channels in the basolateral membrane.


Describe K transport in different regions of the tubule under conditions of high/low K excretion.

See figure 8-1 p 153


Why isn't sodium reabsorption limited to the amount of K present in tubular fluid?

Describe how K is transported into cells (how enters and exits across both membranes)

potassium is actively transported into the cells across both membranes and exits the cells passively across both membranes. It is
pumped into the epithelial cells from the tubular lumen with sodium via Na-K- 2Cl antiporters and from the interstitium via the Na-K-ATPase. As there is far less
potassium than sodium in the lumen, potassium must recycle back to the lumen by passive channel flux to keep a supply of potassium available to run the multiporter with sodium.


What are the two types of cells in the epithelium of the distal nephron?

principal cells (70%)
intercalated cells (type A and type B)

principal cells secrete K at highly variable rates, type A intercalated cells reabsorb K

secretion of K by principal cells involves the uptake of K from the interstitium via the Na-K-ATPase and secretion into the tubular lumen through channels

Type A intercalated cells reabsorb K via the H-K-ATPase in the luminal membrane, which actively takes up K from the lumen and then allows K to enter the interstitium across the BL membrane via K channels

figure 8-2 p 154


Describe the two types of K channels in principal cells of the distal nephron that secrete K in a regulated manner.

Describe when the channels are active/inactive in conditions of low K dietary loads, normal K loads and high loads of K.

ROMK (renal outer medulla)
BK (big capacity to secrete K)

at low dietary loads of K there is no secretion by either kind of channel
(ROMK channels sequestered into intracellular vesicles and BK channels are closed)

at normal K loads, ROMK channels are moved to luminal membrane and secrete K, BK channels still held in reserve and ready to respond when needed

at high excretion rates both channels are present in luminal membrane and avidly secreting K

Figure 8-3 p 156


How does plasma potassium affect potassium excretion?

First, the filtered load is directly proportional to plasma concentration. Second,
the environment of the principal cells, ie, the cortical interstitium, has a potassium concentration that is nearly the same as in plasma. The Na-K-ATPase that takes up potassium is highly sensitive to the potassium concentration in this space, and
varies its pump rate up and down when potassium levels in the plasma vary up and
down. Thus, plasma potassium concentration does exert an influence on potassium excretion, but is not the dominant factor under normal conditions.


Discuss the role of aldosterone in K excretion.

aldosterone is stimulated by elevated level of plasma K
(direct action of K on adrenal cortex and does not involve the RAS)

Aldosterone, as well as increasing expression of the Na-
K-ATPase, also stimulates the expression of ROMK channels in the distal nephron.
Both actions have the effect of increasing potassium secretion. Greater pumping
by the Na-K-ATPase supplies more potassium from the interstitium to the cytosol
of the principal cells, and more ROMK channels provide more pathways for secretion


Describe how delivery of sodium to distal nephron affects K secretion.

any change in Na handling before the distal nephron det. how much is sent on from the TAL (delivered to distal nephron)

Na delivery influences K secretion bc more Na delivered means more Na pumped out by the Na-K ATPase, thus causing more K to be pumped in...the increased K can just recycle back to the interstitium but the usual result is more K secretion


How does distal nephron flow rate affect K secretion?

increased flow detected by mechanosensitive elements of the principal cells (induces intracellular release of calcium and activation of BK channels)

Under most conditions, increased delivery of sodium is the chief cause of increased flow, because sodium is accompanied by water. Thus increased
delivery of sodium implies increased flow.


Describe how concentration of nonchloride anions affects K secretion.

In order for principal
cells to secrete potassium there must be a route (channels) and a driving force (electrochemical gradient).

Under conditions where the reabsorption of sodium is restricted because some of the luminal chloride has been replaced with anions that
are not usually in high concentration and cannot accompany the sodium (because
their permeability is less than that of chloride), one effect is a depolarization of the
luminal membrane (usually described as increasing luminal negativity). This increases
the driving force for potassium secretion.


How does dietary K influence K secretion?

One of the manifestations of changing dietary loads is to regulate the distribution of ROMK channels between the luminal membrane and intracellular storage, ie, high-potassium diets lead to insertion of luminal channels
and therefore higher potassium secretion.

w low K ingestion, few ROMK channels in apical membrane

Another adaptation to prolonged periods of low potassium ingestion is an increase
in H-K-ATPase activity in intercalated cells, resulting in even more efficient reabsorption
of filtered potassium.


If a person is consuming
little salt of any kind (low loads of both sodium and potassium), then we expect, in order to preserve body stores of sodium, to see aldosterone levels high enough to
stimulate avid reabsorption of sodium. But this should also lead to avid secretion
of potassium, which is an unwanted action as the body is also trying to conserve
potassium. How does the body adjust?

potassium cannot be secreted unless there
are open channels. If the actions of intracellular signaling cascades has caused
most of the ROMK channels to be sequestered in intracellular vesicles, then potassium
that is taken up from the interstitium via the Na-K-ATPase recycles back
to the interstitium and is not secreted.


What are diuretics? What are the designated tasks and unwanted side effects?

agents that increase urine volume and reduce ECF volume

Most diuretics,
although effective at their designated task of increasing water and sodium
excretion, have the unwanted side effect of increasing the renal excretion of potassium.


Why is there increased K excretion with the use of diuretics?

potassium reabsorption in the proximal tubule and Henle’s loop is linked to sodium reabsorption. Accordingly, diuretics that act on these sites inhibit not only sodium reabsorption but also potassium reabsorption

However, most of the increased
potassium excretion is due not to this decreased reabsorption but rather to increased potassium secretion by the distal nephron
In all these diuretic states, the
delivery of sodium and the volume of fluid flowing to the distal nephron per unit
time are increased by the upstream inhibition of sodium and water reabsorption.
It is this increased flow and increased delivery of sodium that drives increased
potassium secretion and, hence, excretion

See figure 8-5 p 159


Elevated aldosterone in individuals with heart failure or other diseases of secondary hyperaldosteronism generally does not cause K hypersecretion. Why?

What happens when such persons are treated with diuretics to eliminate their retained sodium and water? How do you prevent the result?

these pt also have low fluid delivery to distal nephron

The diuretics
increase fluid delivery to the distal nephron, and now the patients have
both increased aldosterone and increased flow. This combination tends to cause
marked increases in potassium secretion and excretion. To prevent this combination,
drugs that block the renal actions of aldosterone may be given; such drugs are
weak diuretics because they block aldosterone’s stimulation of sodium reabsorption
(with its small amount of associated water reabsorption). However, unlike
other diuretics, they are “potassium sparing” because they simultaneously block
aldosterone’s stimulation of potassium channels that promote potassium secretion.


Another class of “potassium-sparing” diuretics blocks sodium channels in the principal cells of the cortical collecting duct. How does this work?

this prevents sodium entry from
lumen to cell and effectively prevents the basolateral membrane Na-K-ATPase
pumps from transporting either sodium or potassium and blocks the apical exchange
of sodium for potassium ions. Blocking sodium absorption upstream from the distal nephron increases potassium secretion; however, blocking sodium reabsorption
IN the distal nephron does not


Is elevated plasma pH associated with hypo or hyperkalemia?

the existence of an elevated plasma pH (alkalosis)
is often (ie, frequently but not always) associated with hypokalemia (low plasma
potassium concentration). Similarly, low plasma pH (acidosis) is usually associated
with hyperkalemia.


What are reasons for the effects of acid-base status on potassium?

elevations and depressions in extracellular conc. of hydrogen ions leads to a de facto exchange of these ions w cellular cations (like K)

During an alkalosis, eg, the low extracellular hydrogen
ion concentration induces the efflux of hydrogen ions that are normally bound to intracellular buffers. The loss of the positively charged hydrogen ions is balanced by the uptake of other cations, in this case potassium. Thus, an alkalosis
(with hydrogen ions leaving tissue cells to replenish the loss from the ECF) induces cells to take up potassium, causing a hypokalemia.

Conversely, a low pH (with a concomitant cellular uptake of hydrogen ions) often leads cells to dump potassium, causing a hyperkalemia


How does intracellular pH affect cellular Na-K-ATPase and potassium channel activity?

Low intracellular pH inhibits pumps everywhere, allowing potassium to escape
from cells (particularly muscle cells) to increase plasma potassium

Ordinarily, the increase in plasma potassium would stimulate potassium uptake by the Na-KATPase in principal cells, but low intracellular pH also inhibits the pumps here
as well as luminal membrane potassium channels. Therefore, the principal cells respond inappropriately and do not effectively secrete the excess plasma potassium (paradoxical potassium retention)