9. Regulation of potassium and magnesium Flashcards
What is the main intracellular cation?
potassium
What does potassium determine?
resting membrane potential
What are the body concentrations of potassium?
Total body K+: 3-4mmol/L
• Intracellular fluid: 98%: 150-160mmol/L
• Extracellular fluid: 2%: 4-5mmol/L
What is the effect on resting membrane potential if extracellular K+ rises and falls?
- If extracellular [K+] rises, the resting membrane potential is decreased (i.e. depolarized)
- If extracellular [K+] falls, the resting membrane potential is increased (i.e. hyperpolarized)
Where in the nephron is potassium reabsorbed?
65% in PCT, 20% in TAL
How is potassium reabsorbed in the PCT?
- Passive
- Through tight junctions (paracellular movement)
- Via concentration gradient/solvent drag
How is potassium reabsorbed in the TAL?
- Transcellular - Na+K+ ATPase on basement membrane maintains gradient of Na+ by pumping Na+ out of tubular cell to blood and K+ in. Na+K+Cl- cotransporter on apical membrane transport the ions into the cell. ROMK channels and Cl-K+ channels on the basal membrane move potassium and chloride out of the cell into blood
- Paracellular - ROMK channels on apical membrane also transport K+ out of cell into lumen and the positive charge in lumen repels cations so potassium and other cations move paracellularly to the blood.
Why is there not a lot of reabsorption of potassium in the DCT?
K+ reabsorption and leakage back are approximately equal in early DCT
Where does secretion of K+ occur and in which cells?
In the late DCT and collecting duct
Describe how secretion of K+ occurs
ENaC channels on apical surface move Na into cell. Na+K+ ATPase on basal membrane moves Na into blood and K+ in. the K+ is the then pumped into the lumen through the (ATP dependent) K+ pump
What cells are involved in reabsorption of K+ in late DCt and collecting duct?
intercalated cells
• 10-12% reabsorbed if body trying to preserve K+
Describe how reabsorption of K+ occurs at late DCT and CD
- H+ATPase on apical membrane moves H+ into lumen.
- H+K+ATPase moves H+ into lumen and K+ into cell.
- on the basal surface, Na+K+ ATPase moves K+ out into blood and Na+ into cell
- ROMK channels on basal surface also help move K+ into blood
What are the causes hypokalaemia??
• Excess insulin • Alkalosis • Certain catecholamines (beta-2- adrenergic agonists and alpha- adrenergic antagonists • Insufficient intake - Anorexia nervosa - Prolonged fasting • Too much aldosterone - Primary aldosteronism - Compensated heart failure - Cirrhosis • Diuretics e.g. loop and thiazides • Vomiting • Diarrhoea (lead to metabolic alkalosis) • Sweat – excessive exercise, hot climate
How does alkalosis lead to hypokalaemia?
To lower blood pH K+ moved into cells in exchange for H+
How does increased aldosterone lead to hypokalaemia?
aldosterone causes proliferation of carriers on principal cells so increased secretion
What is the pathophysiology behind hypokalaemia?
- Low K+ results in decreased resting potential – nerve and muscle cells are hyperpolarized
- Less sensitive to depolarizing stimuli and less excitable
- Less action potentials generated and paralysis ensues
Below which levels does hypokalaemia become symptomatic?
Hypokalemia is asymptomatic until K+ concentration falls below 2- 2.5mmol/L
WHat are the Clinical effects of hypokalemia?
- Muscle weakness, cramps and tetany (starts in lower extremities)
- Impaired liver conversion of glucose to glycogen
- Vasoconstriction and cardiac arrythmias
- Impaired ADH action causing thirst, polyuria and no concentration of urine
- Metabolic alkalosis due to increase in intracellular H+ concentration
What is the treatment for hypokalaemia?
treating underlying cause. Oral or intravenous K+ may also be required
What may cause hyperkalaemia?
• Reduced renal excretion • Increased plasma load • Insulin deficiency – Type 1 diabetes • Transcellular shift of K+ out of cells • Pseudohyperkalemia, an artifact: • Certain catecholamines (beta-2- adrenergic antagonists and alpha- adrenergic agonists • Hypoaldosteronism and drugs which reduce effect of aldosterone (renin inhibitors, ACE inhibitors etc.)
What may lead to reduced renal excretion of potassium?
AKI or CKD, mineralocorticoid deficiency (e.g. Addison’s disease), K+ sparing diuretics or renal tubular defects
What may lead to increased plasma load of potassium?
due to dietary changes, IV infusion or cellular tissue breakdown
What may lead to Transcellular shift of K+ out of cells?
due to metabolic acidosis, insulin deficiency, exercise or drugs (digoxin)
What may lead to Pseudohyperkalemia?
due to hemolysis during venipuncture or storage of the sample, a high white cell or platelet count
What are the clinical features of hyperkalaemia?
- Can be asymptomatic
* Muscle weakness, cardiac arrythmias
How is hyperkalaemia treated?
Treatment varies depending on the cause
Emergency treatment of hyperkalemia (>6.5mmol/L or ECG changes)
- Calcium gluconate – Ca2+ stabalises the myocardium, preventing arrythmias
- Insulin – drives K+ into cells to lower plasma concentrations. Given with glucose to avoid hypoglycemia
- Calcium resonium - Removes K+ by increasing excretion from the bowels. Only way to remove K+ without renal replacement therapy
What are other treatments of hyperkalaemia?
• Salbutamol – Drives K+ into cells when given nebulized or IV. Should not be used in patients with ischemic heart disease or arrythmias
• Sodium bicarbonate – Correction of acidosis, would also drive K+ into cells. Not used in patients at risk of
fluid overload
• Renal replacement therapy – Dialysis or hemofiltration are used if medical therapies fail to correct hyperkalemia
What are the ECG signs of hyperkalaemia?
> 5.5 mEq/L = peaked T waves > 6.5 mEq/L = T wave widening and flattening + lengthening PR interval > 7 mEq/L = Widening QRS ~9 mEq/L = sine wave > 9 mEq/L = cardiac arrest
What is the function of magnesium?
- Controls mitochondrial oxidative metabolism and so regulates energy production
- Is vital for protein synthesis
- Regulates K+ and Ca2+ channels in cell membranes
What percentages of magnesium are reabsorbed and where?
- 30% PCT
- 60% LoH
- 5% DCT
- 5% excreted
What is the effect of increased plasma magnesium?
• The Tm for Mg2+ absorption is equal to the concentration of Mg2+ filtered. Therefore an ↑Mg2+ results in ↑filtering which therefore exceeds the Tm. Resulting in an ↑excretion
Where is reabsorption of magnesium regulated?
- Regulation of Mg2+ absorption in LoH.
- If Mg2+ decreases, cell transport of Mg2+ increases
- PTH increases reabsorption of Mg2+ in the LoH
What are the causes of HYPOMAGNESAEMIA?
- Decreased intake
- Diarrhea
- Absorption disorder including fat absorption defects
- Renal wasting – intrinsic (Bartters’s syndrome), extrinsic (diuretics e.g. thiazides)
- Uncontrolled diabetes mellitus – large volume urine flow, carries ions out of nephron
- Excessive alcohol consumption - ↑renal excretion, poor diet
What id Hypomagnesaemia commonly associated with?
- Hypokalemia – many conditions cause low K+ concentrations
* Hypocalcemia – Mg2+ needed to make PTH
What are the signs and symptoms of Hypomagnesaemia >?
• Uncontrolled stimulation of nerves and tetany
Treatment of Hypomagnesaemia
Treatment depends on cause. Oral supplementation or IV/IM magnesium sulphate
cause of Hypermagnesemia
• Renal failure – unable to excrete Mg2+
• Ingestion of Mg2+
- Incorrectly prepared IV infusion
- Mg2+ containing medication (magnesium hydroxide, constipation and heartburn)
signs and symptoms of Hypermagnesemia
- Reduced muscle contraction
- High Mg2+ inhabits PTH release. This leads to hypocalcemia (muscle weakness, diminished reflexes, respiratory failure)
- Very high levels Mg2+ alter the electrical potential across the cardiac cell membrane, lead to cardiac arrythmias
treatment of Hypermagnesemia?
• Treatment depends on cause. Reduce intake. Calcium gluconate injection (Mg2+ and Ca2+ compete). Furosemide to increase excretion. Hemodialysis in severe cases
