8-1: 9/26: Potassium Regulation

Front 1

What factors affect [K+]?

Back 1

Cellular shift (distribution)
Renal excretion

Potassium intake doesn't play a significant role!

Front 2

Potassium is mostly found in the [extracellular/intracellular] compartment.

Back 2

Intracellular

If potassium remained extracellular, you'd go into cardiac arrest.

Front 3

What is the normal range of potassium levels?

Back 3

3.5-5.1 mEq/L

Front 4

How many ions are pumped out/in of the Na-K pump?

Back 4

3Na+ out and 2K+ in, requires an ATP

Front 5

What is the effect of insulin on Na-K-ATPase?

Back 5

Insulin increases pump activity to move K+ into cells

Front 6

What is the effect of catecholamines on Na-K-ATPase?

Back 6

Catecholamines increases pump activity to move K+ into cells

Front 7

What is the effect of plasma potassium concentration on Na-K-ATPase?

Back 7

High plasma potassium concentration increases pump activity to move K+ into cells

Front 8

What is the effect of hyperglycemia on K+ shifts? On intracellular volume?

Back 8

Hyperglycemia increases serum osmolality

H2O leaves cells

Intracellular [K+] increases

K+ diffuses down gradient to extracellular space

As K+ diffuses out of cell, it brings water with it (SOLVENT DRAG)

Front 9

What is the effect of a non-anion gap metabolic acidosis on K+ shifts?

Back 9

Metabolic acidosis: acidic environment

>60% of H+ is buffered in cells (thus, there is increased H+ intracellulary while in an acidotic state)

To maintain electroneutrality, K+ leaves cell as H+ enters; results in diarrhea, renal failure

Front 10

What is the effect of an anion gap metabolic acidosis on K+ shifts?

Back 10

In lactic acidosis or ketoacidosis, anion can enter cell with H+ (anion could be beta-hydroxybuterate, which is negatively charge)

Because both positively (H+) and negatively (beta-hydroxybutyrate) charged molecules are entering the cell, buffering H+ is an electroneutral process

THUS, no need for K+ redistribution.

Front 11

What is the effect of metabolic ALKALOSIS on K+ shifts?

Back 11

HCO3- builds up extracellularly so H+ leaves cells and K+ moves into cells to maintain electroneutrality

Alkalosis decreases extracellular K+ (less prominent effect on extracellular K+ than seen in metabolic acidosis)

Front 12

What is the effect of cell breakdown, such as tumor lysis, hemolysis, rhabdomyolysis on K+ shifts?

Back 12

Causes increased extracellular K+ (cells are spilling K+ out as they lyse)

Front 13

What is the effect of a rapid increase in cell production on K+ shifts?

Back 13

Decreased extracellular K+

Front 14

Describe potassium resorption/filtration as it passes through the nephron. Begin with the glomerulus.

Back 14

K+ freely filtered by glomerulus

Most of K+ passively resorbed in proximal Tubule

Thick ascending limb (20-30%, via Na/K pumps)

Cortical Collecting Duct (<10%, but MOST IMPORTANT)

Front 15

What region of the nephron is most important for K+ regulation?

What cell types are required?

Back 15

Cortical Collecting Duct

Requires principal cells and intercalated cells.

Front 16

Describe the active and passive steps principal cells must take for K+ resorption/excretion.

Back 16

Principal Cells:
1) Get K+ from blood into cell (requires ATP!)
2) Once K+ in cell, need to get it into urine (Passive);
can be due to:
concentration gradient,
electrical gradient (negative charge in lumen will push into urine),
permeability

Front 17

How does plasma K+ concentration affect its secretion?

Back 17

Higher [K+] will inc ATPases and bring more K+ into cell
As intracell K+ rises, more excretion into urine

Front 18

How does a high distal flow rate encourage K+ secretion?

Back 18

High distal flow rate:
As secrete K+, urine flows by in lumen, leaves a lower concentration grad in the lumen. This encourages K+ flow rate into urine (secretion).

Front 19

How does distal sodium delivery encourage K+ secretion?

Back 19

As NaCl is delivered to distal tubule, Na+ resorbed and negative charge (Cl-) left behind.

Cl- absorbed at slower rate and results in negative charge in lumen. This negative charge encourages K+ secretion into lumen (urine).

Potassium-sparing diuretics act here; by blocking Na+ resorption (at ENaC), there's less negative of a charge in the lumen and less K+ is secreted (potassium sparing diuretics)

Front 20

What K+ changes result in aldosterone release?

Back 20

Small rise in serum [K+] can significantly increase aldosterone levels

Aldosterone production decreases with low serum [K+]

NOTE: ALDOSTERONE DEFENDS VOLUME STATUS BY INCREASING Na+ REABSORPTION

Front 21

How does aldosterone increase K+ secretion?

Back 21

Inc activity of Na/K ATPase in basolateral membrane to bring more K+ into cell

Also increases number of Na/K+ channels in luminal membrane

As more Na+ absorbed, more negative lumen, more K+ secretion

Front 22

What cellular changes occur in the kidney when there is a decrease in serum K+?

Back 22

Principal Cells get shut off:
1) Diminished release of aldosterone
2) Fewer K+ and Na+ Channels
3) Decreased permeability to K+ in luminal membrane

1)Diminished release of aldosterone
2) Dec’d NaKATPase activity
3) Dec’d [K+] inside tubule cells
4) Dec’d concentration gradient
5) Dec’d K+ secretion

Front 23

What is the intercalated cell response to a drop in serum [K+]?

Back 23

Intercalated cells increase K+ reabsorption via H+K+ATPase pumps

Front 24

Major causes of hyperkalemia.

Back 24

1) K+ Intake (Rarely the cause)
Iatragenic complication of K+ infusion
PO intake can play a role in chronic kidney dz pts, or pts on ACE-inhibitors

2) Decreased Renal Excretion

3) Decreased Effective Circulating

4) HYPOaldosteronism

Front 25

What nephron changes occur in response to kidney disease?

Back 25

Effect is decreased renal excretion

Amount of K+ excreted per nephron increases

As number of nephrons decrease (scarring), decreased filtered load of K+

Secretion of K+ in Cortical CD decreases

Unless other factors are present, hyperkalemia usually doesn't occur until pts are oliguric (not producing urine)

Front 26

What role does decreased effective circulating volume play in the onset of hyperkalemia?

Back 26

Volume depletion, CHF, cirrhosis decrease Na+ and H2O delivery to CCD and can result in hyperkalemia

Decreased potassium secretion (decreased Na+ absorption-->less negative luminal charge; lower distal flow rate)

Front 27

What medications interfere with aldosterone activity? How?

What effect does this have on K+ levels?

Back 27

Aldosterone inc Na/K ATPase, less K+ in cell, less Na+ channels around, won't have as many K+ channels open

Medications that interfere with productivity/activity of Aldosterone

NSAIDs: Renin Inhibition

**ACE-inhibitors (prevent AgI-->AgII)

**Angiontensin Receptor Blockers (Prevent AgII-->Aldosterone)

Heparin can decrease aldosterone

**Spironolactone directly antagonizes aldosterone

Triamterene, Amiloride block ENaCs

Front 28

Does metabolic acidosis contribute to hyperkalemia in DKA? Why or why not?

Back 28

No, with DKA, there is an anion gap acidosis such that H+ and beta-hydroxybutyrate enter the cell simultaneously and buffer intracellularly. There's no need for K+ to leave the cell, as there is in non-anion gap acidosis where H+ enters the cell, driving K+ out.

Front 29

When do symptoms of hyperkalemia occur?

What EKG findings correlate with hyperkalemia?

Back 29

Symptoms (weakness, paralysis, cardiac arrhythmias) occur when [K+] ≥ 7 mEq/l

EKG will show tall peaked, symmetrical T wave.

Front 30

Treatment of hyperkalemia.

Back 30

Give Calcium

Temporizing measures:
Insulin + glucose (not just temporizing in DKA, it's tx), beta agonist (albuterol), HCO3

Increase Excretion:
Kayexalate (cation exchanger in gut so you don't absorb K+)
IV fluids
Diuretics (block Na+ reabsorption and increase K+ secretion)

Front 31

What is the most appropriate therapy to correct the DKA patient's hyperkalemia?

Back 31

INSULIN followed by K+ replacement to correct total body depletion because likely will have cell shift after K+ gets sucked back into cells/excreted (?)

NO GLUCOSE!!!!

Front 32

Major causes of hypokalemia.

Back 32

Decreased intake (rare)

Increased GI/renal excretion:
-Diarrhea, laxative abuse
-TOO MUCH ALDOSTERONE (adrenal adenoma, b/l adrenal hyperplasia; b/l RAS)
-INCREASED DISTAL URINARY FLOW, NA+ DELIVERY (DIURETICS!)
-Anions in CD lumen (Bicarb, ketones)

Lose HCl, increases serum HCO3 (bicarb), more bicarb filtering and delivered to distal tubule and creates electrical gradient favoring K+ secretion

Cell Shift (catecholamine surge, beta agonists)

Front 33

What are the symptoms of hypokalemia?

Treatment?

Back 33

Syx: Weakness, paralysis, cardiac arrhythmias (K+<2.5)

Tx: Repeatedly replace w/oral/IV preparations--preferably oral, make sure to measure K+ levels and adjust doses