Potassium homeostasis

Question 1

Na+/K+ ATPase pump

Answer 1

• Pumps 3Na+ out and 2K+ into cell
• leads to K+ gradient across cell membrane - high K+ in cell, low K+ outside cell

Question 2

What are the normal levels of potassium?

Answer 2

ECF K+ conc regulated around 4.2 mEq/L
98% total body K+ held in cells
Daily intake 50-200 mEq/L

Question 3

What can occur on the extremes of potassium concentration?

Answer 3

Hyperkalaemia: failure to rapidly remove K+ from the ECF
Hypokalaemia: small loss of K+ from ECF

Question 4

What is the premise of regulation of extracellular potassium concentration?

Answer 4

K+ regulation depends on excretion of kidneys
Redistricbution of K+ between intracellular and extracellular fluid provides first line defence against changes in ECF K+ conc
Cells can provide overflow of K+ during hyperkalaemia and source of K+ during hypokalaemia

Question 5

What is internal potassium balance?

Answer 5

Regulation of K+ balance between intracellular and extracellular space

Question 6

What regulates internal potassium balance in skeletal muscle?

Answer 6

Insulin - postprandial (after eating) release of insulin shifts dietary K+ into cells until kidneys excretes the K+ load
Catecholamines
Leads to K+ uptake via Na+/K+ ATPase pump

Question 7

What factors affect potassium distribution?

Answer 7

Insulin
Aldosterone
B-adrenergic stimulation
Acid-base abnormalities
Cell lysis
Strenuous excercise
Increased extracellular fluid osmolarity

Question 8

How does insulin affect potassium distribution?

Answer 8

Increases cell K+ uptake after eating
If insulin deficient - greater rise in plasma K+ concentration

Question 9

How does Aldosterone affect potassium distribution?

Answer 9

Increases K+ uptake in cells
Increased K+ intake stimulates secretion of aldosterone, increases cell K+ uptake
Excess aldosterone secretion associated with hypokalaemia
Deficient aldosterone production linked to hyperkalaemia due to accumulation of K+ in the extracellular space and renal retention of K+

Question 10

How does B-adrenergic stimulation affect potassium distribution?

Answer 10

Increases cellular uptake of K+
Increased secretion of catecholamines (e.g. adrenaline) causes K+ move from ECF to ICF, by activation of B2-adrenergic receptors
B-adrenergic receptor blockers can cause hperkalaemia

Question 11

How can acid-base abnormalities change potassium distribution?

Answer 11

Metabolic alkalosis - decreases ECF K+ conc
Metabolic acidosis - raises ECF K+ concentration

Question 12

What are the acid-base transport pathways?

Answer 12

Na/H+ exchange via Na+/K+ ATPase
K+ uptake is greater when Na+/H+ exchnage acitivty is stimulated
K+ uptake is diminished when rate of Na+/H+ exchange is reduced

Question 13

What exchange occurs during acidosis with acidemia?

Answer 13

Decrease in extracellular HCO3
-> inhibition of the inward rate of Na+/HCO3 cotransport
-> fall in intracellular Na+ and reduced Na+/K+ATPase activity
Cl/HCO3 exchange also may contribute to apparent K+/H+ exchange
-> decreased extracellular HCO3- ->increased inward movement of Cl- by Cl- HCO3 exchange -> rise in intracellular Cl- -> K+ efflux by K+ Cl- cotransport

Question 14

How may cell lysis affect potassium distribution?

Answer 14

Causes increased extracellular potassium concentration
Cells destroyed -> large amounts of K+ released into the extracellular compartment
Can cause significant hyperkalaemia if many cells destroyed

Question 15

How may strenuous excercise effect potassium distribution?

Answer 15

Can cause hyperkalaemia by releasing potassium from skeletal muscle
Issue if taking B-adrenergic blockers or if insulin deficient

Question 16

How may increased extracellular fluid osmolarity affect potassium distribution?

Answer 16

Increased ECF osmolarity causes osmatic flow of water out of the cells
The cellular dehydration increases intracellular K+ conc -> diffusion of K+ out of the cells -> increasing ECF K+ concentration

Question 17

What factors determines renal K+ excretion?

Answer 17

Rate of K+ filtration
Rate of K+ reabsorption by tubules
Rate of K+ secretion by tubules

Question 18

Where is the tubular handling of potassium in normal conditions?

Answer 18

Most K+ reabsorbed in the proximal tubule
Also reabsorbed in loop of henle most by the thick ascending part - K+ actively cotransported with Na+ and Cl-
Minority absorbed through collecting tubules and collecting ducts - amount reabsorbed here varies depending on the K+ intake

Question 19

What occurs during potassium handling in the proximal tubules and loop of henle?

Answer 19

Proximal tubule cell:
K+ absorption is primarily passive and proportional to Na+ and water
Thick ascending limb of Henle cell:
K+ reabsorption occurs through both transcellular (mediated by K+ transport on apical membrane Na+K+2Cl- cotransporter) and paracellular pathways

Question 20

What role does the principle cells have with potassium in the late distal and cortical collecting tubules?

Answer 20

2 step secretion of K+ from blood:
- uptake from interstitium into the cell by Na+/K+ ATPase pump in basolateral cell membrane -> Na+ out and K+ into cell
- passive diffusion of K+ from in cell into tubular fluid (Na+/K+ ATPase pump creates high intracellular K+ conc = driving force. Luminal membrane of principal cells highly permeable to K+ due to renal outer meduallry K+ channels and big K+ channels)

Question 21

What are the roles of intercalated cells in severe K+ depletion?

Answer 21

• Reabsorption through type A intercalated cells in the distal segments of the nephron
• K+ secretion halted, net reabsorption of K+ in late distal and collecting tubules occurs
• H/K+ ATPase transport mechanism located in luminal membrane:
• K+ reabsorbed in exchange for H+ into tubular lumen
• K+ diffuses through basolateral membrane of cell into blood

Question 22

What role do the intercalated cells have when there is an excess K+ in bodily fluid?

Answer 22

• Type B intercalated cells in late distal tubules and collecting tubules actively secrete K+ into the tubular lumen
• K+ pumped into type B by H+/K+ ATPase pump on basolateral membrane
• K+ diffuses into tubular lumen through K+ channels

Question 23

What three main factors stimulate K+ secretion by the principle cells?

Answer 23

• Increased extracellular fluid K+ concentration
• Increased tubular flow rate
• Increased aldosterone

Question 24

What are the four mechanisms by which increased dietary K+ intake and ECF K+ conc stimulates K+ secretion?

Answer 24

1) Stimulates Na/K+ ATPase pump > increased K+ uptake across basolateral membrane > increased intracellular K+ conc > K+ diffuses across luminal memb into tubule
2) Increases K+ gradient from renal interstitial fluid to interior of the epithelial cell > reduces backleakage of K+ from inside the cells
3) Stimulates K+ channels and their translocation from cytosol to luminal membrane > increases ease of K+ diffusion
4)Stimulates aldosterone secretion by the adrenal cortex > further stimulates K+ secretion

Question 25

How does increased flow rate stimulate potassium secretion? (2)

Answer 25

1) K+ is secreted into tubular fluid > luminal K+ conc increases > reduces driving force of diffusion
With increased tubular flow rate = K+ continuously flushed down tubule > rise in K+ is minimised > net K+ secretion increases
2) High tubular flow rate increases no. BK channels in luminal membrane > increased conductance of K+ across membrane

Question 26

How does increased aldosterone secretion stimulate potassium secretion? (3)

Answer 26

• Increases intracellular K+ conc by stimulating Na+/K+ ATPase activity in basolateral membrane
• Stimulates Na+ reabsorption across luminal membrane > increases electronegativity of lumen > increasing electrical gradient favouring K+ secretion
• increases no. K+ channels in luminal membrane, so increases K+ permeability

Question 27

What is the negative feedback mechanism between extracellular potassium and aldosterone?

Answer 27

Rate of aldosterone secretion from the adrenal gland is controlled by ECF K+ conc
Increases K+ excretion when K+ intake is elevated
Increased K+ intake > increases plasma K+ conc > increases aldosterone (> increases K+ secretion from cort coll tubules) and K+ secretion from cortical collecting tubules > increased K+ excretion

Question 28

How does sodium intake impact potassium homeostasis?

Answer 28

• High Na+ intake > decreases aldosterone secretion > decrease rate of K+ secretion > reduce urinary excretion of K+
• High Na+ intake > High distal tubular flow rate > increases K+ secretion
  = counterbalances each other =little change in K+ excretion

Question 29

What are the expected electrolyte levels if purging?

Answer 29

Chronic vomiting and diuretic use > dehydration > hypovolaemia > hypokalaemia

Question 30

How does purging effect electrolyte levels?

Answer 30

Dehydration > decreased blood volume > activation of RAAS > increased aldosterone secretion > increases expression of H+/Na+ ATPase channels and K+ channels > principle cells of collecting duct > increased urinary K+ losses

Question 31

How do potassium levels affect cardiac function?

Answer 31

• High selective permeability to K+ to other ions generates negative resting membrane potential (Em) this stabilises working atrial and ventricular myocytes during diastole > preventing spontaneous APs from causing premature extrasystoles
• Outside normal K+ range promotes cardiac arrhythmias
  Cellular balances of K+, Na+ and Ca2+ are interlinked through Na+/K+ ATPase and Na+/Ca2+ exchange
  Hypokalaemia and hyperkalaemia will directly impact Na+ Ca2+ and K+ balances

Question 32

How does hypokalaemia affect QT wave?

Answer 32

QT prolongation
Due to slower rate of repolarisation of ventricular myocytes as inhibits conductance of slow delayed-recifier VG K+ channels repsonsible for speeding up the repolarisation of ventricular myocytes
Mechanisms:
- Faster inactivation
- Enhanced Na+ dependent inhibition
- Downregulation of expression of K+ channel