Potassium Homeostasis

Question 1

potassium - roles in cell functions

Answer 1

*creating a potential difference across cell membranes
*critical importance in the function of many cells
*our body has developed mechanisms to manage serum K+:
-regulate total body K+ content
-maintain K+ in proper distributions

Question 2

importance of potassium gradient

Answer 2

*resting membrane potential is maintained by this potassium gradient
*increased or decreased K+ can result in fatal cardiac arrhythmias/EKG changes, muscle weakness, or even paralysis

Question 3

potassium distribution

Answer 3

*HIGH INTRACELLULAR potassium concentration (140-150 mEq/L)
*low extracellular potassium concentration (3.5-5.5 mEq/L)

Question 4

effect of hypokalemia on resting membrane potential

Answer 4

*hypokalemia (low serum K+ levels) → more negative resting membrane potential (hyperpolarizes cell)
*more is needed to reach an action potential

ex: when serum K+ changes from 5 mEq/L (normal) to 2.5 mEq/L, resting membrane potential changes from -90 (normal) → -108

Question 5

effect of hyperkalemia on resting membrane potential

Answer 5

*hyperkalemia (high serum potassium levels) → more positive resting membrane potential (depolarizes cell)
*less is needed to reach an action potential

ex: when serum K+ changes from 5 mEq/L (normal) to 7.5 mEq/L, resting membrane potential changes from -90 (normal) → -79

Question 6

regulation of K+ homeostasis

Answer 6

1. cellular distribution
2. renal excretion
3. GI excretion

note - the KIDNEYS are primarily responsible for maintaining total body K+ content (potassium in = potassium out)

Question 7

internal balance of K+

Answer 7

*immediate buffering of extracellular K+ into and out of skeletal muscle
*skeletal muscle serves as a reservoir to limit the fall of extracellular K+ in certain pathologic conditions
*factors mediating cellular shifts of K+:
1. insulin
2. catacholamines
3. acid-base status
4. plasma tonicity

Question 8

effects of INSULIN on extracellular K+ (simple)

Answer 8

*insulin shifts K+ INTO CELL by inserting or activating Na+/K+ ATPase pumps
*leads to decreased serum potassium

Question 9

effects of INSULIN on extracellular K+ (detailed)

Answer 9

1. insulin binds its receptor
2. binding → phosphorylation of IRS-1
3. IRS-1 binds PI3-K
4. IRS-1/PI3-K complex activates PDK1
5. two different outcomes:
   a. activates Akt- pathway to INSERT GLUT4
   OR
   b. activates aPKC to INSERT Na+/K+ ATPase pumps (→ insulin shifts K+ into cells)

Question 10

effects of CATECHOLAMINES on extracellular K+ (simple)

Answer 10

*beta2 stimulation shifts K+ INTO cells
*results in decreased serum potassium

Question 11

effects of CATECHOLAMINES on extracellular K+ (detailed)

Answer 11

beta2 stimulation → increases Na+/K+ ATPase pump ACTIVITY via cAMP and PKA-dependent pathway → shifts K+ into cells

Question 12

effects of INORGANIC ACIDS on extracellular K+ (simple)

Answer 12

mineral acidosis (inorganic acids) shifts K+ OUT OF CELLS

Question 13

effects of inorganic acids on extracellular K+ (detailed) - 2 mechanisms

Answer 13

1. mineral acidosis decreases pH → decreases rate of NHE1 and NBCe → decreases intracellular Na+ → decreases Na+/K+ ATPase activity → NET CELLULAR LOSS OF K+
2. fall in extracellular HCO3- → increases Cl- influx by Cl-HCO3- exchanger → enhances K-Cl transporter → INCREASES K+ EFFLUX

Question 14

effects of ORGANIC ACIDS on extracellular K+

Answer 14

organic acids have NO EFFECT ON EXTRACELLULAR K+

Question 15

effects of PLASMA TONICITY on extracellular K+

Answer 15

increased tonicity (hyperosmolarity) → increased H2O movement OUT OF CELLS → H2O movement favors K+ efflux via solvent drag → cell shrinkage leading to increased intracellular K+ → creation of a concentration gradient for K+ efflux

Question 16

factors that drive K+ INTO cells

Answer 16

1. insulin
2. beta 2 stimulation (catecholamines)
3. alkalosis

Question 17

factors that drive K+ OUT OF cells

Answer 17

1. insulin deficiency
2. beta-ANTAGONISTS
3. acidosis
4. hyperosmolarity
5. cell lysis
6. severe exercise
7. digitalis

Question 18

handling of potassium in the PROXIMAL TUBULE

Answer 18

*bulk of K+ is reabsorbed in proximal tubule
*very little regulation occurs in response to diet

*2 mechanisms of K+ reabsorption:
1. PASSIVE PARACELLULAR REABSORPTION (primary):
-active Na reabsorption drives net fluid reabsorption in PT cells
-K+ reabsorption through SOLVENT DRAG
-proportional to Na+ and H2O
2. paracellular pathway:
-luminal voltage shifts from slightly negative to slightly positive
-ADDS FURTHER DRIVE for K+ reabsorption in distal part of proximal tubules

Question 19

potassium handling in the THICK ASCENDING LOOP OF HENLE

Answer 19

*2 mechanisms of K+ reabsorption:
1. transcellular (primary):
-Na+/K+ ATPase maintains a low intracellular [Na+], which provides favorable drive for the NKCC cotransporter
-apical ROMK channel provides pathway for K+ to recycle from cell to lumen to provide adequate supply to sustain NKCC cotransporter
2. paracellular:
-movement through ROMK provides the slightly positive lumen needed for paracellular K+ reabsorption

note - absorption can be reversed if given loop diuretic or high K+ load

Question 20

potassium handling in early DISTAL TUBULE

Answer 20

*K+ SECRETION begins in DT and progressively increases into CCD
*SECRETION OF K+ occurs via:
1. ROMK
2. electroneural K+/Cl- cotransporter

Question 21

potassium handling in the PRINCIPAL CELLS of the CCD

Answer 21

*primarily responsible for K+ SECRETION

Question 22

factors regulating K+ secretion

Answer 22

1. distal delivery of Na+
2. luminal flow rate
3. aldosterone presence
4. extracellular [K+]

Question 23

effects of distal Na+ delivery on K+ secretion

Answer 23

*increased distal delivery of Na+ → K+ SECRETION
-diuretics, volume expansion, high Na+ diet

*decreased distal delivery of Na+ → LESS K+ secretion
-prerenal states, obstruction, low Na+ diets

*ENaC inhibitors → LESS K+ secretion

Question 24

effects of tubular flow rate on K+ secretion

Answer 24

*increased flow rate → decreased luminal [K+] → K+ SECRETION

*low flow states (i.e prerenal states/obstruction) → LESS K+ secretion

Question 25

effects of aldosterone on K+ secretion

Answer 25

*aldosterone → INCREASED K+ SECRETION

aldosterone → increases Na+/K+ ATPase expression/activity → increases ENaC expression/activity → activates ROMK channels → K+ secretion

Question 26

effects of extracellular [K+] on K+ secretion

Answer 26

increased serum (extracellular) K+ concentration → directly stimulates aldosterone → INCREASED K+ SECRETION

Question 27

potassium handling in the INTERCALATED CELLS of the CCD

Answer 27

*primarily responsible for K+ REABSORPTION via active H+/K+ ATPase

Question 28

clinical manifestations of hypokalemia

Answer 28

*symptoms tend to be proportionate to the degree & duration of hypokalemia
1. cardiac arrhythmias (very interpatient dependent)
2. muscle weakness
3. renal manifestations
4. hyperglycemia

Question 29

EKG findings of hypokalemia

Answer 29

*slightly prolonged PR interval
*slightly peaked P wave
*ST depression
*shallow T wave
*PROMINENT U WAVE

Question 30

causes of hypokalemia

Answer 30

*poor intake (not really a problem)
*pseudohypokalemia (AML patients)
*shifts - hyperinsulinemic, beta agonists, alkalosis
*excess excretion:
1. excess renal excretion - drugs, hormones, mag depletion, kidney issues (increased RAAS activation → increaased excretion of K+)
2. excess non-renal excretion - skin excretion, GI excretion (diarrhea, vomiting, etc)

Question 31

clinical manifestations of hyperkalemia

Answer 31

*muscle weakness or even paralysis
*cardiac manifestations:
-EKG changes
-conduction abnormalities/arrhythmias (RBBB, LBBB, sinus brady, VT, VF, etc)

Question 32

EKG findings of hyperkalemia

Answer 32

*TALL, PEAKED T WAVES
*shorted QT interval
*widening of QRS complex
*loss of P → sine wave

Question 33

causes of hyperkalemia

Answer 33

*excessive intake - dietary, K+ supplements, salt substitutes
*pseudohyperkalemia - traumatic venipuncture, CLL, thrombocytosis
*shifts - metabolic acidosis, insulin deficiency, beta blockers, digoxin overdose, cell lysis, exercise, hyperosmolarity
*decreased excretion - renal impairment, drugs/conditions that affect RAAS cascade