Lect 14: Regulating Plasma K+

Question 1

Extracellular K is tightly regulated in the plasma in a normal range of

Answer 1

3.5 - 5 mM but it is the outwardly directed K gradient. Na is low inside the cell and K is low outside of the cell

Question 2

Why is K+ important?

Answer 2

that K+ gradient across the cell membrane is the major determinant of the potential or voltage difference across the cell membrane in both electrically excitable and unexcitable cells….certain tissues need these currents for the excitability (such a s cardiac tissue, neurons etc.

Question 3

What organ maintains K+ balance?

Answer 3

the balance is maintained by the renal handing of K by the kidneys which increase or decrease K excretion to match increases and decreases in K+ consumption

Question 4

the positive charge carried by the movement of the cation, K+ across the cell membrane may arise from passive, protein-mediated transport, or simple diffusion

Answer 4

The positive charge carried out of the cell by K current through membrane channels is the dominant ionic current determining the inside-negative cell membrane potential difference….for a certain K+ conc, the potential difference across the cell membrane (-60mV) is very close to the K+ equilibrium potential

Question 5

Hyperkalemia - increased k+ conc in plasma (>5)

Answer 5

decreases the magnitude of the outwardly directed K+ conc gradient, decreasing the contribution of the gradient to the cell membrane potential–> less negative potential difference in both excitable and non-excitable cells

Question 6

What happens to cells/organs as a result of hyperkalemia

Answer 6

when hyperkalemia occurs in excitable cells, electrical signaling is or impulse propagation is disturbed and may cause hyperexcitable muscle contraction, in heart–>uncontrolled muscle spasm–>cardiac arrest

Question 7

Which type of acidosis can be cause by hyperkalemia?

Answer 7

metabolic acidosis because of the effective exchange of intracellular H+ for extracellular K+ across cell membranes, which adds acid (H+) to the plasma - more K+ want to go into the cell, so more H+ will come out.

Question 8

Hypokalemia - decrease in plasma K+ so more K+ will want to flow out of the cell (outward gradient increased). What happens to the inside negative potential? difference?

Answer 8

it goes up because more K+ is leaving the cell

Question 9

How would hypokalemia affect excitable organs?

Answer 9

it would weaken muscle contraction (muscle hypoexcitability) –> if this happens in the lungs, they won’t get adequately perfused and you would go into respiratory failure

Question 10

Which kind of metabolic syndrome could hypokalemia?

Answer 10

METABOLIC ALKALOSIS - because as K+ is rushing out of the cell, H+ are rushing back into the cell and less is around int he blood so you drop H+ conc and you get alkalosis

Question 11

External K+ balance

Answer 11

since K consumption is variable, the kidney must increase or decrease excrete of it accordingly…in order tot keep the plasma ECF constant

kidneys and feces…colon excretes 10% of ingested K+

Question 12

Internal K+ balance

Answer 12

is regulated by the Na/K ATPase…keeps plasma K+ in balance….needs to be maintained because 1% shift in intracellular K+ would increase plasma [K+] by 50%

Question 13

Increased uptake of K+ into cells is the first line of defense against hyperkalemia

Answer 13

plasma levels of K rises because of the food we eat and it could be from their release of diseased or injured cells. To compensate for this, the cell sequesters it inside. Upregulating Na/K ATPase synthesis.
–>insulin, epinephrine and aldosterone promote an increased cellular uptake of K+ and a shift from EC fluid into cells.

Question 14

Why do diabetics have to watch their K intake

Answer 14

RBC do not have a nuclsus and therefore cannot upregulate synthesis of Na/K ATPase to protect it from hyperkalemia. So the dysregulation of insulin release and circulating levels of insulin in poorly conteolled diabetes mellitus may compromise the tolerance of diabetic patients to a K+ load and predispose them to hyperkalemia

Question 15

Acidemia inhibits the Na/K ATPase and the Na/K/2Cl co-transporter causing loss of K+ from cells, resulting in hyperkalemia

Answer 15

acidosis - lots of H+ in blood will want to push H+ into cells and cause K+ to rush out of cells causing hyperkalemia.

alkalosis - not enough H+ in the blood so H+ rush out of the cell and K+ rushes in….causing hypokalemia

Question 16

Acidemia—> hyperkalemia

Answer 16

When H+ conc is high outside of the cell, it gets pumped into the cell. The intracellular conc of H+ now increases, inhibiting the Na/K ATPase and the Na/K/2Cl co-transporter. This decreases K+ uptake into the cell via both transporters, which decreases intracellular K as well as increases exctracellular K possibly causing hyperkalemia

—opposite is true

Question 17

Decreased cellular uptake of H+ and efflux of H+ will occur when plasma H+ conc decreases.

Answer 17

The resulting decrease in intracellular H+ conc dis-inhibits or stimulates the Na/K ATPase as well as the Na/K/2Cl co-transporter. This dis-inhibition or stimulation increases K+ uptake into the cell via the Na/K/ATPase and the Na/K/Cl co-transporter, which both increases intracellular K+ as well as decreases extracellular K+ possibly causing hypokalemia

Question 18

If you inject a person with a bolus of K+ their plasma conc will increase initially but then it will decrease. The first line of defense against hyperkalemia is to

Answer 18

increase its uptake into cells. The increase is detected by a change in membrane potential within minutes! By 1) release of aldosterone from the adrenal cortex 2) release of epinephrine from the adrenal medulla 3) release of insulin from the pancreas. They completely mitigate the rise in K+ within an hour…so it is buffered

Question 19

Reabsorption of K+ in the kidney in the proximal tubule is constitutive (80%) and LH (10%)

Answer 19

So the fraction of K+ filtered does not change when the plasma K+ conc is increased or decreased, whether or not you have hypo or hyperkalemia

Question 20

It is the distal nephron (late distal tubule and cortical collecting duct) that reabsorbs K+ and secretes it,.

Answer 20

Reabsorption or secretion depends on the plasma conc. if plasma conc is below normal it will be reabsorbed; if it is above normal then it will be secreted

Question 21

How do you handle K+ when dietary intake is low and K balance is negative?

Answer 21

When K+ balance is negative (too little in diet), increased K+ reabsorption in the distal tubule restores K balance.

==>despite a compensating increase in K+ reabsorption, hypokalemia may result from chronic dietary K+ deficiency.

Question 22

K+ excretion is regulated either by
1. INCREASING K+ REABSORPTION from the remaining 10% of filtered K+ entering the distal nephron, which decreases K+ excretion when in negative K+ balance

Answer 22

2. by DECREASING REABSORPTION from the remaining 10% of filtered K entering the distal nephron
3. secreting additional K+ into the tubular fluid of the distal nephron, both of which increase K excretion when in positive K+ balance

Question 23

Handling K+ when intake is too much

Answer 23

secretion by the distal nephron increases…it may increase to levels sufficient 10 - 150% of the filtered load. The compensatory increase in k+ excretion results from a decrease in K+ reabsorptoin as well as from a secretion of K+ into the distal nephron

Question 24

Which two segments are K+ excretion not regulated?

Answer 24

proximal tubule and loop of Henle

Question 25

K+ reabsorption in the proximal tubule

Answer 25

PARACELLULAR (P and P) | ==> occurs by solvent drag and by passive electro-diffusion

Question 26

In the early proximal tubule

Answer 26

active transcellular Na (SODIUM) transport resulting from uptake across the lumen and efflux across the basolateral membrane drives net fluid reabsorption by osmosis transcellularly and via a paracellular pathway between cells. A flow of K+ is entrained in the flow of fluid between cells driven by osmosis and is described as a process of solvent drag. K is dragged from the TF into the interstitial fluid

Question 27

In the LATE proximal tubule

Answer 27

transepithelial voltage changes from lumen negative to lumen positive and this provides an electrical driving force "pushing" movement of K+ through the paracellular pathway. Simple electro-diffusion describes the process of paracellular transfer of K+ in the late proximal tubule `

Question 28

K+ Absorption the Thick AL occurs by both transcellular and paracellular transport

Answer 28

Paracellular pathway: a lumen positive voltage difference across the tubule epithlium drives K+ passively through the paracellular pathway by diffusion. The positive charge is made from K+ channels effluxing it out. The negative charge on the basoalateral side is made by Cl- being pumped out and this draws K+ into the interstitium

Question 29

K+ Absorption the Thick AL occurs by both transcellular and paracellular transport

Answer 29

Transcellular Transport: transporters Lumenal transporters: Na-K-2Cl co-transporter gets these thing uptaken into the cell Basolateral: ion-specific efflux (Na/K ATPase and Cl and K+ channels

Question 30

The presence of K+ channels in the lumen mediates efflux of a small amount of intracellular K back into the TF, which together with Cl efflux across the basolateral membrane

Answer 30

generates a lumen positive potential difference across the TAL tubular epithelium. The lumen positive potential difference also seves as a driving force for K, Na, Ca and Mg reabsorption across the TAL epithelium

Question 31

Transcellular K+ Reabsorption in the Distal Nephron

Answer 31

occurs via the alpha-intercalated cells of the Initial Collecting tubule, CCT and medullary collecting tubule ==> occurs via active transport of the K/H+ ATPase pump--> pumps K+ into the cell in exchange for H+ transported out Cl/HCO3 exchanger in the basolateral membrane mediates efflux of intracellular HCO3 to the basolateral membrane causes HCO3--> to go out to the interstitium

Question 32

Increase in HCO3 absorption occuring simultaneously with increased K+ reabsorption may induce a secondary metabolic alkalosis (increased plasma HCO3) when K+ reabsorption is maximal to reverse the deficit in plasma K (hypekalemia)

Answer 32

This is hypokalemic metabolic alkalosis. When plasma K+ is low, the cell-to-plasma shift of K+ from cells and the plasma to cell shift may exacerbate the metabolic alkalosis

Question 33

Secretion of K+ may be

Answer 33

1. Flow dependent and Na dependent. 2. Secretion occurs via the principal cells of the initial collecting tubule (ICT) and the CCT. 3. Transcellular- Na/K brings it in and then it passively diffuses out of the cell across the luminal membrane through K+ channels and by co-transport of K+ and Cl

Question 34

Flow dependence of K secretion: high flow rate

Answer 34

the lumenal cells (prinicipal cells) membrane are permeable to K. it has lots of K+ channels for them to exit the cell through. When the flow is high or fast, it prevents the tubular fluid accumulation and concentration of K+ from rising. It maintains the steep, instde-to-outside TF across the membrane. K is swept away as fast as it is transported out of the cell so with it swept away more of it will be secreted from the cell.

Question 35

Flow dependence of K secretion: low flow rate

Answer 35

at low flow rates, efflux of K accumulates to higher conc at the membrane surface, which decreases the magnitude of the inside-to-outside gradient driving the passive efflux of K+ from the cells to the TF across the lumenal membrane. According, a decreased rate of K+ efflux across the lumenal membrane will occur across the membrane which in turn decreases the rate of transcellular K+ secretion

Question 36

Na reabsorption is coupled to K+ secretion

Answer 36

If Na is high then this will stimulate its reabsorption. but at the same time, it will increase K+ secretion, which increase K+ loss and poassible hypokalemia

Question 37

Increased distal nephron secretion of K+

Answer 37

increased plasma K+ upregulates K+ by the BASOLATERAL membrane Na/K ATPase 2. increased driving force for K+ transport across the apical membrane 3. decreased distal nephron reabsorption - when K+ conc is high, aldosterone is high, and thus the expression of membrane transport proteins mediating transcellular transfer of K+ is increased, increasing the capacity of the distal nephron to secrete K+

Question 38

What two thing stimulate aldosterone?

Answer 38

Angiotensin II and increased plasma K+ - increased lumenal Na conductance depolarizes luminal membrane potential, thus increasing the driving force for efflux across the luminal membrane - Aldosterone upregulates transcription of the enzymes necessary for Na reabsoroption and K+ secretion -->when you are in negative K+ balance, what happens to your aldosterone levels: decreased (because you don't want ot be secreting K+ when you don't have any to begin with)

Question 39

Alkalosis increases distal nephron K+ secretion

Answer 39

``` increased pH (decreased H+) -->K+ goes in In the distal nephron, increased intracellular increases the driving force and rate of K+ transport across the lumen--> more K+ secreted: hypokalemia (hypokalemic metabolic alkalosis) ``` --opposite is true ( you get alkalosis)