Potassium Balance Flashcards
Describe the intra- and extracellular concentrations of potassium.
~150 mmol/L within the cells
~4.5 mmol/L outside of the cells
What is the difference in potassium maintained by?
Na/K ATPase
What maintains the low ECF [K+]?
- Internal balance
- Shifts K+ between the ECF and ICF compartments.
What are the major factors that affect potassium balance?
Diet
Urine
Stools
Sweat
What does external balance refer to?
Balance between what is taken in via the diet and what is excreted out
What organs control external balance?
Kidneys
What does the regulation of K+ homeostasis imply?
ACUTE REGULATION
CHRONIC REGULATION
How is acute regulation achieved?
Distribution of K+ through the ECF and ICF compartments
How is chronic regulation achieved?
Kidney adjusting K+ excretion and reabsorption
List some of the functions of potassium.
- determines the ICF osmolality, and thus cell volume
- determines the resting membrane potential (RMP)
- affects vascular resistance
Describe the significance of the Na+-K+ ATPase pump.
- Establishes a net charge across the plasma membrane
- Interior of the cell is negatively charged with respect to the exterior.
What is the importance of resting potential?
- Prepares the nerve and muscle cells for the propagation of action potentials
- For nerve impulses and muscle contraction.
What does the accumulation of sodium ions outside of the cell allow?
- Draws water out of the cell
- Maintain osmotic balance
What is the importance of an osmotic balance?
Without it, cell would swell and burst from the inward diffusion of water
What is the boundary for hypokalaemia?
plasma [K+] < 3.5 mM
What is the boundary for hyperkalaemia?
plasma [K+] > 5.5 mM
What is the Nerst equation?
E = RT/zF ln[X]o/[X]i
E is the Nerst Equilibrium Potential, R is the ideal gas constant, T is the temperature in Kelvin, z is the charge of the ion (valance) and F is Faraday’s number.
How are membrane potentials formed?
Creation of ionic gradients (ie. the combination of chemical and electrical gradients).
What can be determined from the Nerst equation?
Determine at which point the chemical and electrical gradients balance each other
What happens the plasma [K+] is altered above or below normal?
- Severely affect the heart (cardiac cell depolarisations and hyperpolarisations)
- Produces changes in ECG.
How does [K+] affect action potentials?
low [K+] = hyperpolarisation
high [K+] = depolarisation
How does hyperkalaemia affect ECG readings?
- increased QRS complex
- increased amplitude of the t wave
- eventual loss of the P wave
How does hypokalaemia affect ECG readings?
- lowered amplitude of the T wave
- prolonged Q-U interval
- prolonged P wave
Describe hypokalaemia.
Caused by a renal or extra-renal loss of K+ or by the restricted intake of K+.
What cases are linked to hypokalaemia? Briefly give a reason for each case. PART 1
- long-standing use of diuretics without KCl compensation
- hyperaldosteronism/ Conn’s Syndrome (increased aldosterone secretion)
What cases are linked to hypokalaemia? Briefly give a reason for each case. PART 2
- prolonged vomiting, which leads to Na+ loss, which leads to increased aldosterone secretion, which leads to K+ excretion by the kidneys
- profuse diarrhoea (diarrhoea fluid contains 50 mM of K+)
What does hypokalaemia lead to?
Decreased release of adrenaline, aldosterone and insulin
Why is acute hyperkalaemia normal following exercise?
Kidneys will excrete the extra K+ easily
What cases are linked to diseased hyperkalaemia?
- insufficient renal excretion
- increased release of K+ from damaged body cells (eg. during chemotherapy, long-lasting hunger or prolonged exercise )
- long-term use of potassium-sparing diuretics
What is a life-threatening plasma [K+]? Give a reason why.
Plasma [K+] of > 7mM. Can lead to cardiac arrest
What can be used to drive K+ influx to reverse hyperkalemia?
- Insulin/ glucose infusion
- Hormones (such as aldosterone and adrenaline) by stimulating Na/K pump
Describe the renal handling of Na+ and K+.
- Kidneys are designed to conserve Na and excrete K.
- Na+ and K+ are filtered freely at the glomeruli. Thus, the plasma and the GF have the same [Na+] and [K+].
Which drugs can increase the risk of hyperkalemia?
Drugs like β-blockers and ACE inhibitors by raising serum [K+]
Which drugs can enhance the risk of hypokalemia?
Loop diuretics - for heart failure
Is K+ excretion in stools under regulatory control?
No
Describe K+ movement in the PCT. PART 1
- K+ reabsorption is passive and paracellular through tight junctions.
- Na+/K+ pump in cell membranes maintains high intracellular [K+]
- Many K+ channels through which ions leak out.
Describe K+ movement in the PCT. PART 2
- By the end of the early proximal tubule, essentially, all the glucose amino acids has been reabsorbed.
- Establishes a Cl- and K+ concentration gradient from the lumen to the peritubular fluid. - Na+ and K+ move passively along this gradient with Cl- in a paracellular route.
What can happen if the Na/K pump is inhibited?
- Na gradient is dissipated
- Loss of primary Na transport and the associated secondary active solute transport.
- No osmotic gradient for water transport.
What can inhibit the Na/K pump?
Dopamine
Describe Na+/K+ movement in the Loop of Henle. PART 1
- Loop of Henle creates a cortico-medullary osmotic concentration gradient
- Hence, as the fluid enters the descending limb and water leaves, the fluids get more concentrated
- As it enters the ascending limb, characteristic changes occur and it is now impermeable to H2O but highly permeable to solutes.
Describe Na+/K+ movement in the Loop of Henle. PART 2
- In the thin ascending limb, Na and Cl diffuse out.
- In the thick ascending limb, active reabsorption/ pumping of Na and Cl out of the fluid occurs, thereby making it more dilute.
Describe Na+/K+ movement in the Loop of Henle. PART 3
- Thick ascending limb movement done via a Na/2Cl/K symporter on the luminal membrane, which is driven by the [Na] gradient.
- Entry of Na from the Na-H antiporter.
- On the basolateral side, we have Na/K ATPase pump and the cotransport of Cl and K out of the cell (especially in the thick ascending limb).
Describe Na+/K+ movement in the Loop of Henle. PART 4
- Some diffusion of K back into the descending limb.
- No water movement, the fluid in the lumen is very diluted, when it reaches the distal tubule, it is very hyposmotic
Describe K+ movement in the DCT. PART 1
- Majority reabsorbed.
- But, in order to balance the input and output, need to be able to excrete excess K into the tubule.
- Most of this occurs mainly in the principal cells of the distal tubule and collecting duct.
- Variation in K excretion not due to reabsorption in PCT and Loop of Henle
Describe K+ movement in the DCT. PART 2
- K would enter the secreting cells from the blood via the Na-K-ATPase pump.
- Diffuses from the cell down the electrochemical gradient through K+ channels that exist in the luminal/ apical membrane into the tubular fluid.
- Electric gradient across the luminal membrane normally opposes the exit of K from the cell
- Gradient is reduced by the Na flux through the ENaC channel in that membrane (which, like the Na+/K+ transporter, is aldosterone-sensitive).
Describe K+ movement in the DCT. PART 2
- Chemical gradient dominates.
- K+ secretion is coupled with Na+ reabsorption, ie. the more Na+ reabsorbed by the principle cell, the more K+ secreted.
- K-Cl cotransporter (symporter) also exists in the apical membrane and transports both K and Cl from the cell into the lumen.
What causes the switch between K secretion and reabsorption?
- activity of the Na-K-ATPase pump
- electrochemical gradient
- permeability of the luminal membrane channel
What determines K+ secretion in the DCT?
- increased K+ intake
- changes in blood pH (alkalosis and acidosis)
How is aldosterone involved in K+ secretion? PART 1
- Increase the activity of the Na+/K+ pump, which increases K+ influx, which increases intracellular [K+], which contributes to the cell-lumen concentration gradient
- Increases ENaC channels, which increase Na+ reabsorption, which decrease cell negativity and increase lumen negativity, thus contributing to the voltage gradient
How is aldosterone involved in K+ secretion? PART 2
- Redistributes ENac from its intracellular localisation to the membrane
- Increases the permeability of the luminal membrane to K+
How does plasma [K] affect K+ secretion?
- Slows k+ exit from the basolateral membrane, so increases intracellular [K+], so contributing to the cell-lumen concentration gradient
- Increased activity of Na+/K+ ATPase, so increased [K+] within the cell
- Increased plasma [K], so stimulated aldosterone secretion
How does alkalosis affect K secretion?
- Increased activity of the Na+/K+ pump
- Increased [K+] in the cell - favours the concentration gradient for K secretion.
- Increase in tubular fluid pH
- Increases the permeability of the luminal membrane.
Why does tubular pH increase during alkalosis?
- Proximal tubule H+ secretion is decreased
- Increases HCO3- in the tubular fluid
- Greater tubule pH
How does ACUTE acidosis affect K secretion?
- Increase in [H+] of the ECF
- Reduces the activity of the Na+/K+ pump
- Decreases intracellular [K]
- Reducing the passive diffusion and excretion of K.
How does an increase in tubular flow rate affect K+ secretion?
- Secreted K is sweeped away
- Tubular fluid [K] low
- Rapid rate of net secretion
- Maintains the [K+] gradient favourable to secretion.
How does ADH affect K+ secretion?
- Increases the K conductance of the luminal membrane.
- Stimulates secretion
- Effect is not as great as that of aldosterone.
Where does the reabsorption of K+ occur and what is its role?
- Mainly in the intercalated cells (late DCT and CD)
- Under normal conditions, it doesn’t play much of a role since most of the reabsorption occurs in the PCT and LoH.
- Intercalated cells may have a H/K-ATPase pump with H excretion, resulting in K reabsorption - active in severe hypokalaemia.
How are people with hypokalaemia affected by changes in K+ reabsorption activity?
- Distal tubule, the connecting tubule, and the cortical collecting duct do not secrete K+, and may reabsorb some K+.
- K+ which passes through the cortical collecting duct is reabsorbed in the medullary collecting duct
- K+ excreted in the urine is minimal.
How is K excretion maintained with a fall in ECFV?
- Increased Na and fluid reabsorption in the PCT
- Decreased distal K secretion because of reduced delivery of fluid and Na to the principal tubule cells.
- Stimulates the release of aldosterone, which stimulates distal potassium secretion.
- Change in potassium excretion is minimised.
How does the RAAS system affect K secretion in a patient with low blood pressure? PART 1
- JGA senses the fall in local BP
- Macula densa detects the low sodium concentration in the DCT.
- Release of renin, which leads indirectly to the formation of Angiotensin II.
- Causes vasoconstriction and stimulates the adrenal cortex to produce aldosterone.
How does the RAAS system affect K secretion in a patient with low blood pressure? PART 2
- Aldosterone acts on the DCT to increase Na reabsorption by increasing insertion of Na/K ATPase pumps, and ENaC channels.
- Incoming Na+ brings more water via osmosis, thus restoring fluid volume and pressure.
- Greater K+ (or H+) secreted in exchange.
- Aldosterone increases both the recovery of Na and the loss of K+ (or H+).
How does the RAAS system affect K secretion in a patient with low blood pressure? PART 3
- High plasma [K+] causes the release of aldosterone from the adrenal cortex.
- Renin release is supressed by direct negative feedback from Angiotensin II.
- Aldosterone also acts on the intercalated cells to increase the activity of the Na+/H+ antiporter
- Influences the acid-base status by increasing H+ secretion - increase in serum pH.
Describe Adisson’s Disease as a pathology related to Na and K balance.
- Damage to adrenal cortex, so there is less hormone production
- Deficiency in aldosterone, which leads to the body secreting large amounts of Na (leaving low serum Na levels) and the body retaining K (leading to hyperkalaemia).
What is the treatment for Adissons’s Disease?
Corticosteroid (steroid) replacement therapy for life.
What is Conn’s Syndrome?
Primary aldosteronism - due to an aldosterone-producing adenoma of the zona glomerulosa of the adrenal gland.
How does Conn’s Syndrome cause hypokalaemia?
- Increase in plasma aldosterone
- Increase Na+ reabsorption and K+ excretion, so hypertension develops.
- Increases the fluid volume, leading to hypokalaemia, hypernatremia (high serum sodium levels), and alkalosis.
What is the treatment for Conn’s Syndrome?
- Surgical removal of the tumor-containing adrenal gland
- Hypertension and hypokalaemia are controlled with K+-sparing agents (eg. spironolactone).
What does the adrenal cortex produce?
→ Glucocorticoid hormones
→Sex hormones
What factors shift K+ out of cells?
→ Insulin deficiency
→ Aldosterone deficiency
→ Acidosis
→ Strenuous exercise
→ Increased ECF osmolarity
What factors shift K+ into cells?
→ Insulin
→ Aldosterone
→ Alkalosis
What does an increase in tubule fluid flow rate result from?
→ increased GFR or inhibition of reabsorption upstream or diuretics
What inhibits eNAC channels?
Diuretics
How is K+ maintained at high levels within the kidney cells?
→ Sodium travels from the tubular lumen to the ECF bringing glucose with it
→the Na+ and K+ pump maintains this on the basolateral side
→ Maintains K+ at high levels in the kidney cells
What happens to the equilibrium potential when you have hyperkalaemia?
→ Less negative
What happens to the equilibrium potential when you have hypokalaemia?
→ More negative
What happens to K+ concentration after a meal?
→ Increase in plasma K+
→ shifted into ICF compartment
What hormones is the ICF K+ shift due to?
→ insulin
→ adrenaline
→ aldosterone
