Regulation of K+, Ca2 and PO4- Flashcards
True or false: Kidneys excrete the amount of Ca2+ and Pi that comes from the diet.
Technically…false. They excrete the amount that is absorbed by the intestinal tract. Reason for this is because normal bone remodeling does not result in a net gain or loss of Ca2+ or Pi. It results in release and reuse of the same amount of Ca2+ and Pi. Also, body fluids contain certain normal levels of these compounds (just like Na+) so there shouldn’t be any need to replace any of these things if we are in steady state balance.
Aldosterone secretion is increased by […] and […] and decreased by […] and […]
Aldosterone secretion is increased by hyperkalemia and by angiotensin II (after activation of the renin-angiotensin system). Aldosterone secretion is decreased by hypokalemia and natriuretic peptides released from the heart
If a person has hyperkalemia, what is the effect of giving them calcium gluconate?
Calcium gluconate raises the threshold of excitability of the membrane, making it harder to reach threshold. Since hyperkalemia makes the membrane more excitable, moving the setpoint for threshold decreases the rapid firing seen with hyperkalemia
- What does a diuretic do to the body?
- How does it accomplish this?
- Why would you put someone on a diuretic?
What drives Ca2+ reabsorption in the DCT?
This is regulated by PTH levels.
In the distal tubule, where the voltage in the tubule lumen is electrically negative with respect to the blood, Ca++ reabsorption is entirely active because Ca++ is reabsorbed against its electrochemical gradient. Thus Ca++ reabsorption by the distal tubule is exclusively transcellular. Calcium enters the cell across the apical membrane by a Ca++-permeable ion channel (TRPV5). Inside the cell, Ca++ binds to calbindin-D28k. The calbindin-Ca++ complex carries Ca++ across the cell and delivers it to the basolateral membrane, where it is extruded from the cell primarily by the 3Na+/Ca++ antiporter (NCX1)
What affect does plasma [Ca2+] have on renal excretion/reabsorption of Ca2+?
Hypercalcemia activates the CaSR in the thick ascending limb of Henle’s loop, inhibiting Ca++ reabsorption in this segment, which results in an increase in urinary Ca++ excretion and thereby reduces plasma [Ca++]. Hypocalcemia has the opposite effect
- What hormones control levels of plasma K+?
- What effect do they all have?
- If increase in K+ is acute, what do these hormones cause?
- If increase in K+ is chronic, what do these hormones cause?
- Epinephrine
- Insulin
- Aldosterone
- Increase K+ uptake into skeletal muscle, liver, bone, and red blood cells by stimulating Na+-K+-ATPase, the Na+-K+-2Cl− symporter, and the Na+-Cl− symporter in these cells
- Acute stimulation of K+uptake is mediated by an increased turnover rate of existing transporters
- Chronic increase in K+ uptake is mediated by an increase in the quantity of Na+-K+-ATPase.
What affects the [K+] in the ECF?
Dietary intake
Exchange with ICF
Urinary excretion
In very basic terms, how do the following diuretics work:
- Loop diuretics
- Thiazide diuretics
- K+ sparing diuretics
What effect will an increase in plasma osmolality have on K+ balance between ECF and ICF?
If K+ is leaving cells can lead to hyperkalemia
80% of phosphate that is filtered is [reabsorbed or secreted] in the […] part of the nephron.
Reabsorbed
Proximal tubule
How does epinephrine cause uptake of K+ into cells?
Epinephrine can either cause K+ release or uptake depending on which receptors it interacts with. Epinephrine is a catecholamine, so it binds to adrenergic receptors.
- Stimulation of α-adrenoceptors releases K+ from cells
- Stimulation of β2-adrenceptors promotes K+ uptake by cells
Why does hyperosmolality of ECF cause an increase in K+?
As plasma osmolality increases, water leaves cells because of the osmotic gradient across the plasma membrane. Water leaves cells until the intracellular osmolality equals that of the ECF. This loss of water shrinks cells and causes the cell [K+] to rise. The rise in intracellular [K+] provides a driving force for the exit of K+ from cells
How does aldosterone affect kidney secretion of K+?
- Increasing the amount of Na+-K+-ATPase in the basolateral membrane which facilitates K+ uptake across the basolateral membrane into cells and thereby elevates intracellular [K+]
- Increasing the expression of the sodium channel (ENaC) in the apical cell membrane. Increased Na+ in the cell depolarizes the apical membrane voltage. The depolarization of the apical membrane and increased intracellular [K+] enhance the electrochemical driving force for K+ secretion from the cell into the tubule fluid. Taken together, these actions increase the cell [K+] and enhance the driving force for K+ exit across the apical membrane
- Elevating serum glucocorticoid stimulated kinase (Sgk1) levels, which also increases the expression of ENaC in the apical membrane and activates K+channels
- Stimulating channel activating protease 1 (CAP1, also called prostatin), which directly activates ENaC
- Stimulating the permeability of the apical membrane to K+ by increasing the number of K+ channels in the membrane
What affect does acute metabolic acidosis (from organic acids, like lactic acid, keto acids, etc.) have on K+ levels in plasma?
Leads to hyperkalemia
How is Pi reabsorbed in the nephron?
What are some changes that are seen in EKGs in a person with hyperkalemia?
The first sign of hyperkalemia is the appearance of tall, thin T waves on the ECG. Further increases in the plasma [K+] prolong the PR interval, depress the ST segment, and lengthen the QRS interval on the ECG. Finally, as the plasma [K+] approaches 10 mEq/L, the P wave disappears, the QRS interval broadens, the ECG appears as a sine wave, and the ventricles fibrillate
If you ingest a meal with K+, what happens to levels of insulin, aldosterone and epinephrine in response?
A rise in the plasma [K+] that follows K+absorption by the gastrointestinal tract stimulates insulin secretion from the pancreas, aldosterone release from the adrenal cortex, and epinephrine secretion from the adrenal medulla.
What drives Ca2+ reabsorption in the PCT?
Ca++ reabsorption by the proximal tubule occurs primarily via the paracellular pathway. This passive, paracellular reabsorption of Ca++ is driven by the lumen-positive transepithelial voltage across the second half of the proximal tubule and by a favorable concentration gradient of Ca++, both of which are established by transcellular sodium and water reabsorption in the first half of the proximal tubule.
Why can loop diuretics lead to hypocalcemia?
They inhibit the Na+/K+/2Cl- transporter in TAL, which leads to less removal of (-) charge from urine, so there’s less driving force for Ca2+ and other (+) charged ions to diffuse across to blood via paracellular route.
They can be used to treat hypercalcemia.
Under the affects of aldosterone, K+ is […] into the […].
Secreted
Cortical collecting duct
What are some changes seen in EKG with hypokalemia?
Hypokalemia prolongs the QT interval, inverts the T wave, and lowers the ST segment on the ECG.
What role do the kidneys play in regulating Ca2+ and PO4- levels in the plasma?
Regulate total body Ca++ and Pi by excreting the amount of Ca++ and Pi that is absorbed by the intestinal tract (normal bone remodeling results in no net addition of Ca++ and Pi to the bone or Ca++ and Pi release from the bone)
What are some factors that can lead to hypokalemia?
What are some that can lead to hyperkalemia?
What happens to K+ in the plasma and excretion with exercise?
How do K+ sparing diuretics (spironolactone) work?
Explain this diagram.
If a person ingests 80mEq of K+, 72 will be absorbed in the gut and 8mEq will be excreted in the feces. Of the 72 that is absorbed, it will equilibrate with the ECF to restore any loses of ECF K+ to keep ECF [K+] at 70mEq since that is tightly regulated, exchange if necessary to restore ICF K+, in healthy person there’s no need to replenish so all 72mEq from diet is excreted in urine
What drives Ca2+ reabsorption in the loop of henle?
Ca++ reabsorption by the loop of Henle also occurs primarily via the paracellular pathway. Like the proximal tubule, Ca++ and Na+ reabsorption in the thick ascending limb parallel each other. These processes are parallel because of the significant component of Ca++ reabsorption that occurs via passive, paracellular reabsorption secondary to Na+ reabsorption that generates a lumen-positive transepithelial voltage
How does the handling of K+ vary throughout the various parts of the nephron?
PCT and Loop of Henle can only reabsorb K+ and they do so passively, so there is a constant amount of K+ that is reabsorbed here regardless of whether a person is in need of K+. See image for percents.
In DCT and CD, these areas can either reabsorb or secrete K+ depending on the [K+] in ECF. If the person is depleted, then they will reabsorb through intercalated cells. If the person is normal or increased K+ they will secrete through principal cells. The amounts that they secrete or reabsorb vary widely based on demand.
Diuretics cause an increase in excretion that is coupled by an increase in flow rate. What effect does increasing flow rate have on the secretion of K+?
- Increased flow bends the primary cilium in principal cells, which activates the PKD1/PKD2 Ca++ conducting channel complex. This mechanism allows more Ca++ to enter principal cells and increases intracellular [Ca++]. The increase in [Ca++] activates BK+ channels in the apical plasma membrane, which enhances K+ secretion from the cell into the tubule fluid.
- As flow increases, so does the Na+ concentration of tubule fluid. This facilitates Na+ entry across the apical membrane of distal tubule and collecting duct cells, thereby decreasing the interior negative membrane potential of the cell. This depolarization of the cell membrane potential increases the electrochemical driving force that promotes K+ secretion across the apical cell membrane into tubule fluid. In addition, increased Na+ uptake into cells activates the Na+-K+-ATPase in the basolateral membrane, thereby increasing K+ uptake across the basolateral membrane and elevating cell [K+].
What affect does chronic metabolic acidosis (from organic acids, like lactic acid, keto acids, etc.) have on K+ levels in plasma?
Leads to hypokalemia
Don’t worry too much about details, but essentially chronic increased H+ (metabolic) leads to chronic increased plasma K+ which triggers chronic aldosterone release which rapidly works to decrease K+ in plasma leading to increased K+ secretion and excretion and hypokalemia
What effect does cell lysis (traumatic muscle injury or extreme muscle strain) have on K+ in plasma and secretion in kidney?
True
K+ is reabsorbed by intercalated cells in the nephron. Describe the process of reabsorbing K+.
α-Intercalated cells reabsorb K+ by an H+-K+-ATPase transport mechanism located in the apical membrane that takes in K+ in exchange for H+. K+ exit from intercalated cells into the blood is mediated by a K+ Cl- symporter channel.
Reabsorption of K+ is activated by a low-K+ diet.
- The PCT reabsorbs […]% of Pi filtered by the glomerulus.
- By what means does it reabsorb Pi?
- The proximal tubule reabsorbs 80% of the Pi filtered by the glomerulus. The loop of Henle, distal tubule, and the collecting duct reabsorb negligible amounts of Pi. Therefore approximately 20% of the Pi filtered across the glomerular capillaries is excreted in the urine.
- Pi reabsorption by the proximal tubule occurs by a transcellular route (Figure 9-9). Pi uptake across the apical membrane of the proximal tubule occurs via two Na+-Pi symporters (IIa and IIc). Type IIa transports 3Na+ with one divalent Pi (HPO−24), and carries positive charge into the cell. Type IIc transports 2Na+ with one monovalent Pi (H2PO−4) and is electrically neutral. Pi exits across the basolateral membrane by a Pi-inorganic anion antiporter that has not been characterized.
Describe the amount of reabsorption of Ca2+ by the different areas of the nephron.
K+ is screted by principal cells in the nephron. Describe the process of secreting K+ from the blood to the filtrate.
K+ is uptaken from the blood across the basolateral membrane by action of the Na+-K+-ATPase. This creates a high intracellular [K+], which provides the chemical driving force for K+ to diffuse from the cell into the tubular fluid through either the ROMK+ channels, which are essentially always open, or a K+-Cl− symporter in the apical plasma membrane.
Although K+ channels also are present in the basolateral membrane, K+preferentially leaves the cell across the apical membrane and enters the tubular fluid due to two reasons: (1) the electrochemical gradient of K+ that favors its downhill movement into the tubular fluid and (2) the permeability of the apical membrane to K+ is greater than that of the basolateral membrane.
2
The K+ gradient is maintained by Na+/K+ ATPase pumps and is tightly regulatd. Why is it so important to maintain this gradient at specific levels?
- If the ECF has low [K+] (hypokalemia), then there will be an even higher driving force for K+ to leave the cell, leading to increased hyperpolarization of the membrane. This makes it more difficult for excitatory impulses to reach threshold to generate an AP. It also delays the reactivation of Na+ channels causing a longer period of time bewteen APs.
- If the ECF has high [K+], then there will be a smaller driving force for K+ to leave the cell, leading to insufficient hyperpolarization. This makes it easier for excitator impulses to reach threshold and generate an AP and shortens the time it takes for Na+ channels to reactivate between APs, thus shortening the time between.
How does high dietary intake of K+ regulate K+ secretion in the kidney?
- Hyperkalemia stimulates Na+-K+-ATPase and thereby increases K+ uptake across the basolateral membrane. This uptake raises the intracellular [K+] and increases the electrochemical driving force for K+ exit across the apical membrane.
- Hyperkalemia also increases the permeability of the apical membrane to K+.
- Hyperkalemia stimulates aldosterone secretion by the adrenal cortex, which acts synergistically with the plasma [K+] to stimulate K+ secretion.
- Hyperkalemia also increases the flow rate of tubular fluid, which stimulates K+ secretion by the distal tubule and collecting duct
What is the effect of respiratory acidosis?
What is the effect of respiratory alkalosis?
In what forms can Ca2+ be found in the blood?
How does pH influence these ratios?
Acidemia increases the percentage of ionized Ca++ at the expense of Ca++bound to proteins, whereas alkalemia decreases the percentage of ionized Ca+
Since the PCT and loop of henle can only reabsorb K+, what is the mechanism by which they do this?
Just pay attention to the very bottom K+ that is gong between the cells from lumen to blood. That’s PCT and loop of henle. Other things in image are not.
Reabsorbed
Secreted
