6. K+ ion regulation

Question 1

describe the distribution of K+ ions

Answer 1

intracellular: 145 mM (90%)
extracellular: 4.5 mM (2%)

Question 2

which 2 methods are used to regulate [K+]ecf

Answer 2

1. internal: exchange of ECF and ICF K+ (rapid) via Na/K ATPase
2. external: variable urinary K+ excretion (6-8hrs)

Question 3

name 4 factors which can increase K+ mov. from ECF into cells

Answer 3

K+ movement into cells depends on activity of Na/K ATPase - activity is increased by:

1. increased K+ conc. in plasma
2. insulin - increased after meal, aiding mov. of K+ rapidly added to ECF by alimentary tract into ICF (T1DM Ps can become hyperkalaemic following meal in absence of proper insulin therapy)
3. noradrenaline activation of B2 adrenoRs (salbutamol B2 R agonists used in asthma can cause hypokalaemia)
4. aldosterone

Question 4

describe the K+ movement in nephron tubules that remains constant

Answer 4

1. PCT: K+ reabsorption (65%) via paracellular route (driven by lumen +ve charge)
2. TAL: K+ reabsorption (25%) via NKCC2 symporter

Question 5

describe where the nephron can alter K+ mov. to regulate [K]ecf

Answer 5

1. DCT:
   - if normal/high K+: K+ secretion (10-50%)
   - if low K+: K+ reabsorption (3%)
2. CD:
   - if normal/high K+: K+ secretion (5-30%) via passive transport through principal cell luminal K+ channels (+ basolateral Na/K ATPase)
   - if low K+: K+ reabsorption via luminal H/K ATPase on a-intercalated cells (+ basolateral K+ channel)

Question 6

describe how CD K+ secretion is increased in hyperkalaemia

Answer 6

1. increased [K]ecf… increased principal cell basolateral Na/K ATPase activity… increased [K]i causing INCREASED ELECTROCHEMICAL GRADIENT… increased K+ secretion
2. increased [K]ecf… INCREASED ALDOSTERONE SECRETION from adrenal glands… increased principal cell basolateral Na/K ATPase and luminal ROMK… increased K+ secretion (main mechanism)
3. HIGH DISTAL TUBULAR FLOW RATE: any secreted K+ washed away… K+ concs. build up relatively late in tubule… high electrochemical gradient for outward diffusion through tubule… increased K+ secretion by principal cells

Question 7

explain the aldosterone paradox

Answer 7

Ability of kidney to stimulate NaCl retention with minimal K+ secretion under conditions of volume depletion, and to maximise K+ secretion without Na+ retention in hyperkalaemia (despite stimulation of principal cell basolateral Na/K ATPase in both occasions).

• Volume depletion: decreased distal fluid flow rate… blunts any aldosterone-mediated increase in K+ secretion
• Volume expansion: decreased aldosterone doesn’t interfere with K+ homeostasis as increased tubular flow increases K+ secretion

Question 8

explain why [K+]ecf disturbances affect membrane potential

Answer 8

Low [K+]ecf important for maintaining steep K+ ion gradient across cell membranes - largely responsible for membrane potential of excitable and non-excitable cells.

Hypokalaemia: low serum [K]… increased intracellular : extracellular K+ gradient… increased membrane excitability… hyperpolarisation… decreased cell contraction

Hyperkalaemia: high serum [K]… decreased intracellular : extracellular K gradient… increased depolarisation… inactivation of some voltage-gated Na+ channels… decreased membrane excitability… decreased cell contraction

[K]ecf disturbance can thus cause severe probs. in nerve conduction and muscle contraction, e.g. potentially life-threatening cardiac arrythmias.

Question 9

do metabolic acidosis and alkalosis cause hyper- or hypokalaemia? explain why

Answer 9

1) Majority of body cells contain H/K antiporter which exchanges H+ with K+.
- Metabolic acidosis: large plasma H+ increase… H+ influx into cells and K+ efflux out… hyperkalaemia
- Metabolic alkalosis: large plasma H+ decrease… H+ efflux from cells and K+ influx… hypokalaemia

2) Acute acid-base changes in ECF can also cause modulation of principal cell K+ secretion (unclear why):
- Metabolic acidosis: decreased K+ secretion
- Metabolic alkalosis: increased K+ secretion

Question 10

how will [K]ecf change in a respiratory acidosis

Answer 10

no change in [K]ecf as build up of acid (as CO2) can diffuse through cell membranes rather than requiring antiporter transport

Question 11

name 5 symptoms of hypokalaemia, and 2 symptoms of hyperkalaemia

Answer 11

1- weakness (decreased skeletal muscle contraction)
2- constipation and resp. depression (decreased smooth muscle contraction)
3- polyuria (decreased K+ causes ADH resistance)
4- arrhythmias and cardiac arrest

Hyperkalaemia:
1- weakness (decreased skeletal muscle contraction)
2- arrhythmias and cardiac arrest

Question 12

describe the plasma K+ changes in hypo- and hyperkalaemia

Answer 12

hypokalaemia = <3.5 mmol/L 
hyperkalaemia = >5.5 mmol/L

Question 13

describe different causes for internal and external K+ balance shifts causing hypokalaemia

Answer 13

Internal balance shifts:
1- excess insulin: increased Na/K ATPase activity
2- increased beta-adrenergic activity (e.g. B-adrenoR agonists like salbutamol): increased Na/K ATPase activity
3- metabolic alkalosis: increased activity of H/K antiporter which transports H+ out and K+ into cells

External balance shifts:
1- decreased dietary intake (eg fasting, anorexia)
2- increased GI loss: vomiting or diarrhoea
3- increased urine loss: increased aldosterone (volume depletion, primary and secondary aldosteronism), increased UO, renal tubular acidosis, Mg2+ deficiency
(*loop or thiazide diuretics)

Question 14

describe the ECG changes caused by hypokalaemia

Answer 14

caused by delayed ventricular repolarisation:

1. prolonged QT interval
2. ST depression
3. flat T wave
4. U wave

Question 15

how should hypokalaemia be treated

Answer 15

• oral K+ supplements

- slow IV K+

Question 16

describe different causes for internal and external K+ balance shifts causing hyperkalaemia

Answer 16

Internal balance shifts:

1. insulin deficiency: decreased Na/K ATPase activity
2. decreased B-adrenergic activity (eg B-adrenoR antagonists)
3. metabolic acidosis: increased cellular H+ uptake causes K+ efflux
4. hyperosmolarity (eg dehydration): increased H2O efflux causes increased [K+]i so K+ efflux down conc. gradient
5. cell lysis: direct release of massive ICF K+ store, eg burns, rhabdomyolysis, haemolysis or rapid tumour cell lysis in chemotherapy
6. strenuous exercise: skeletal muscle APs require large effluxes of intracellular K+ into extracellular space

External balance shifts:

1. increased K+ intake (eg IV fluids)
2. decreased UO:
   
   • hypoaldosteronism or drugs that decrease aldosterone (renin inhibitors, ACEi, AngIIi, K+ sparing diuretics)
   • AKI

Question 17

describe the ECG changes caused by hyperkalaemia

Answer 17

1. widened QRS complex with decreased R wave amplitude
2. ST depression
3. narrow peaked T wave
4. wide flat P wave
5. prolonged PR interval

Question 18

describe the treatment for hyperkalaemia

Answer 18

1. Ca2+: stabilises myocardial cell membrane
2. insulin, glucose, B-adrenoR agonists, sodium bicarbonate: shifts K+ into cells
3. resins: bind K+ for elimination in GI tract
4. K+ wasting diuretics: K+ elimination in kidneys
5. dialysis (severe cases)