Potassium Balance Flashcards
1
Q
Describe the intra- and extracellular concentrations of potassium.
A
~150 mmol/L within the cells
~4.5 mmol/L outside of the cells
2
Q
What is the difference in potassium maintained by?
A
Na/K ATPase
3
Q
What maintains the low ECF [K+]?
A
- Internal balance
- Shifts K+ between the ECF and ICF compartments.
4
Q
What are the major factors that affect potassium balance?
A
Diet
Urine
Stools
Sweat
5
Q
What does external balance refer to?
A
Balance between what is taken in via the diet and what is excreted out
6
Q
What organs control external balance?
A
Kidneys
7
Q
What does the regulation of K+ homeostasis imply?
A
ACUTE REGULATION
CHRONIC REGULATION
8
Q
How is acute regulation achieved?
A
Distribution of K+ through the ECF and ICF compartments
9
Q
How is chronic regulation achieved?
A
Kidney adjusting K+ excretion and reabsorption
10
Q
List some of the functions of potassium.
A
- determines the ICF osmolality, and thus cell volume
- determines the resting membrane potential (RMP)
- affects vascular resistance
11
Q
Describe the significance of the Na+-K+ ATPase pump.
A
- Establishes a net charge across the plasma membrane
- Interior of the cell is negatively charged with respect to the exterior.
12
Q
What is the importance of resting potential?
A
- Prepares the nerve and muscle cells for the propagation of action potentials
- For nerve impulses and muscle contraction.
13
Q
What does the accumulation of sodium ions outside of the cell allow?
A
- Draws water out of the cell
- Maintain osmotic balance
14
Q
What is the importance of an osmotic balance?
A
Without it, cell would swell and burst from the inward diffusion of water
15
Q
What is the boundary for hypokalaemia?
A
plasma [K+] < 3.5 mM
16
Q
What is the boundary for hyperkalaemia?
A
plasma [K+] > 5.5 mM
17
Q
What is the Nerst equation?
A
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.
18
Q
How are membrane potentials formed?
A
Creation of ionic gradients (ie. the combination of chemical and electrical gradients).
19
Q
What can be determined from the Nerst equation?
A
Determine at which point the chemical and electrical gradients balance each other
20
Q
What happens the plasma [K+] is altered above or below normal?
A
- Severely affect the heart (cardiac cell depolarisations and hyperpolarisations)
- Produces changes in ECG.
21
Q
How does [K+] affect action potentials?
A
low [K+] = hyperpolarisation
high [K+] = depolarisation
22
Q
How does hyperkalaemia affect ECG readings?
A
- increased QRS complex
- increased amplitude of the t wave
- eventual loss of the P wave
23
Q
How does hypokalaemia affect ECG readings?
A
- lowered amplitude of the T wave
- prolonged Q-U interval
- prolonged P wave
24
Q
Describe hypokalaemia.
A
Caused by a renal or extra-renal loss of K+ or by the restricted intake of K+.
25
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)
26
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+)
27
What does hypokalaemia lead to?
Decreased release of adrenaline, aldosterone and insulin
28
Why is acute hyperkalaemia normal following exercise?
Kidneys will excrete the extra K+ easily
29
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
30
What is a life-threatening plasma [K+]? Give a reason why.
Plasma [K+] of > 7mM. Can lead to cardiac arrest
31
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
32
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+].
33
Which drugs can increase the risk of hyperkalemia?
Drugs like β-blockers and ACE inhibitors by raising serum [K+]
34
Which drugs can enhance the risk of hypokalemia?
Loop diuretics - for heart failure
35
Is K+ excretion in stools under regulatory control?
No
36
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.
37
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.
38
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.
39
What can inhibit the Na/K pump?
Dopamine
40
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.
41
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.
42
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).
43
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
44
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
45
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).
46
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.
47
What causes the switch between K secretion and reabsorption?
- activity of the Na-K-ATPase pump
- electrochemical gradient
- permeability of the luminal membrane channel
48
What determines K+ secretion in the DCT?
- increased K+ intake
- changes in blood pH (alkalosis and acidosis)
49
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
50
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+
51
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
52
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.
53
Why does tubular pH increase during alkalosis?
- Proximal tubule H+ secretion is decreased
- Increases HCO3- in the tubular fluid
- Greater tubule pH
54
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.
55
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.
56
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.
57
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.
58
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.
59
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.
60
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.
61
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+).
62
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.
63
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).
64
What is the treatment for Adissons's Disease?
Corticosteroid (steroid) replacement therapy for life.
65
What is Conn's Syndrome?
Primary aldosteronism - due to an aldosterone-producing adenoma of the zona glomerulosa of the adrenal gland.
66
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.
67
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).
68
What does the adrenal cortex produce?
→ Glucocorticoid hormones
→Sex hormones
69
What factors shift K+ out of cells?
→ Insulin deficiency
→ Aldosterone deficiency
→ Acidosis
→ Strenuous exercise
→ Increased ECF osmolarity
70
What factors shift K+ into cells?
→ Insulin
→ Aldosterone
→ Alkalosis
71
What does an increase in tubule fluid flow rate result from?
→ increased GFR or inhibition of reabsorption upstream or diuretics
72
What inhibits eNAC channels?
Diuretics
73
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
74
What happens to the equilibrium potential when you have hyperkalaemia?
→ Less negative
75
What happens to the equilibrium potential when you have hypokalaemia?
→ More negative
76
What happens to K+ concentration after a meal?
→ Increase in plasma K+
→ shifted into ICF compartment
77
What hormones is the ICF K+ shift due to?
→ insulin
→ adrenaline
→ aldosterone
