Disorders of Potassium Balance Flashcards
What is the intracellular concentration of potassium in the body?
150 mEq/L
What maintains the large potassium gradient across the cell membrane?
Na+-K+-ATPase
What are the cutoffs for hyperkalemia and hypokalemia?
[K+] > 5 mEq/L is hyperkalemia
[K+] < 3.5 mEq/L is hypokalemia
What is the major effect of potassium imbalance?
hyperkalemia causes the membrane potential to become less negative
hypokalemia causes the membrane potential to become more negative
What is the normal range of potassium in the plasma?
3.5-4.9 nM
What hormones promote the uptake of K+ into cells?
epinephrine and insulin
increased uptake by stimulating the Na+-K+-ATPase pump
act within a few minutes
insulin is the most important
causes of hypokalemia
excess insulin - stimulates Na+/K+ ATPase
beta adrenergic agonists - stimulates Na+/K+ ATPase
acute illness (MI, head injury) - catecholamine stimulation of Na+/K+ ATPase
hypokalemic periodic paralysis - mutations in cation channels
alkalemia - stimulates Na+/K+ ATPase
major pathophysiologic factors influencing the distribution of K+ between the ICF and ECF
acid-base balance
plasma osmolality
cell lysis
exercise
How does acid-baes balance affect potassium distribution?
metabolic acidosis increases plasma K+
metabolic alkalosis decreases plasma K+
How does plasma osmolality affect potassium distribution?
increased osmolality increases K+ release by cells
decreased osmolality ddecreases K+ release by cells
How does exercise affect potassium distribution?
K+ is released from skeletal muscle
causes of hyperkalemia
beta adrenergic blockade - inhibits Na+/K+ ATPase
digitalis toxicity - inhibits Na+/K+ ATPase
intense exercise - activates K+ ATP channel
acidosis - inhibition of Na+/K+ ATPase and activation of K+ channels
hyperosmolality (hyperglycemia) - water rich in K+ exits the cells because of osmolar effect
What is the distribution of K+ reabsorption in the nephron?
67% reabsorbed in the PT
about 20% absorbed by the loop of Henle
reabsorption is a constant fraction of the amount filtered
10% to 50% in the DCT
5% to 30% in the CCD
What is the process of K+ transport in the distal tubule and collecting duct?
1) K+ uptake across the basolateral membrane by Na+-K+ ATPase
2) diffusion of K+ from the cell into the tubular fluid, operation of Na+-K+ ATPase pump creates a high tracellular [K+], which provides the chemical driving force for K+ exit across the apical membrane through K+ channels
What are the major factors that control the rate of K+ secretion by the distal renal tubule and the collecting duct?
the activity of the Na+-K+ ATPase in the collecting tubule
the driving force for K+ in the apical membrane, influenced by urine flow rate
the ability of K+ to cross the apical membrane via a K+ channel called RMK
the ability of Na+ channels to function, creating a favorable electrical gradient for potassium secretion
aldosterone which increases the activity of the Na+-K+ ATPase pump and opens the sodium channel
major physiologic regulators of K+ secretion
plasma [K+}
aldosterone
distal Na+ delivery
Describe the mechanisms in a principle cell for potassium excretion
ROMK K+ channels and ENaC Na+ channels on the apical membrane
Na+-K+ ATPase and K+ channels on the basolateral membranes
factors that perturb K+ secretion
levels of circulating aldosterone in pathological states such as excess (increased K+ secretion) or deficiency (decreased K+ secretion)
flow of tubular fluid and distal sodium delivery and urine flow
acid-base balance - alkaloses increases K+ secretion an dacidosis decreases K+ secretion
amiloride
a diuretic that blocks sodium channels in the CCD
has the same effect as decreasing nluminal Na+
indirectly decreases K+ secretion
ECG findings of hyperkalemia
P wave flattened
PR interval prolonged
QRS complex widens
ventricular fibrillation or aystole leading to cardiac arrest may occur at high levels
extrarenal causes of hyperkalemia
tissue damage and factors that modify transcellular distribution of potassium and result in a shift of potassium from the intracellular to the extracellular fluid compartment
renal causes of hyperkalemia
decreased GFR (reduced to less than 10 mL/minute) when the mechanisms fail
aldosterone deficiency - most commonly caused by diabetes and interstitial renal disease, drugs blocking RAAS and NSAIDs can also lead to this, as well as chronic heparin therapy
decreased distal Na delivery or blockade of Na channels in the cortical collecting tubule
distal Na delivery or blockade of Na channels in the cortical collecting tube - best characterized in patients with chronic obstructive nephropathy with damage to collecting duct cells interfering with both H+ and K+ secretion
potassium-sparing diuretics such as amiloride or triamterene also interfere with sodium transport and directly inhibit potassium secretion, spironolactone can cause it as well
factors affecting adrenal aldosterone release
angiotensin II +++
K+ ++
ACTH +
ANP -
Dopamine -
causes of selective aldosterone deficiency (normal cortisol)
low plasma renin activity - hyporeninemic hypoaldosteronism
normal plasma renin activity - normoreninemic hypoaldosteronism, cyclosporin A
iatrogenic causes of renal hyperkalemia
NSAIDs
ACE inhibitors
ARBs
chronic heparin therapy
cyclosporin A
FK506 (tacrolimus)
spironolactone
drugs that cause decreased distal Na+ delivery or blockade of Na+ channels in the CCT
amiloride
triamterene
trimethoprim
pentamidine
acquired diseases that lead to problems with potassium excretion
chronic obstructive nephropathy - damage to CCD cells that impair H+ and K+
sickle cell disease
systemic lupus erythematosus
What level of hypokalemia are symptoms usually seen at?
~2.5 mEq/L
plasma K may only be slightly reduced even with substantial body K+ depletion
ECG changes associated with hypokalemia
increased AV conduction time
diminished QRS voltage
ST segment depression, widening, flattening
inversion of T waves
appearance of U waves
depletional vs. nondepletional hypokalemia
depletional - low boy potassium from normal or extra renal losses
nondepletional - normal body potassium from transcellular redistribution
What are some sources for extra renal loss of K+?
inadequate intake
copious sweat losses
GI tract losses such as vomiting, diarrhea, etc.
reasons for renal losses of K+
mineralocorticoid excess
glucocorticoid excess
diuretics
Barter’s syndrome
Gitelman’s syndrome
renal tubular acidosis
causes for hypokalemia associated with metabolic acidosis
diarrhea
renal tubular acidosis type I and II
ureteral diversions to the GI tract
causes of hypokalemia associated with metabolic alkalosis
vomiting
diuretics
Berter’s syndrome
Gitelman’s syndrome
causes of hypokalemia associated with normal or low blood pressure
diuretics (thiazide and loop diuretics)
proximal and distal tubular acidosis
Barter’s syndrome
Gitelman’s syndrome
hypomagnesemia
drug-induced (aminoglycosides, cisplatin)
causes of hypokalemia associated with hypertension
primary and secondary hperaldosteronism
Cushing’s syndrome
pseudohyperaldosteronism
licorice
Liddle’s syndrome
primary vs secondary hyperaldosteronism
primary - plasma renin low, plasma aldosterone high, secondary to adenoma, hyperplasia, and adrenal carcinoma
secondary - plasma renin and aldosterone high, secondary to renovascular disease
Cushing’s syndrome
excess cortisol causes hypokalemia
mechanism of licorice in hypokalemia
11 beta hydroxysteroid dehydrogenase deficiency
Liddle’s syndrome
defect in Na+ channels in the DCT, where they are open more often
features of Barter’s Syndrome
hypokalemia, urinary K+ wastage
metabolic alkalosis
normal or low BP
increased plasma renin and aldosterone
increased urinary prostaglandins
hyperplasia of juxtaglomerular apparatus
resistance to exogenous angiotensin II infusion
urinary calcium normal or increased
plasma Mg2+ normal or low
features of Gitelman’s
milder phenotype compared to Barter’s
hypokalemia, urinary K+ wastage
metabolic alkalosis
normal or low BP
increased plasma renin and aldosterone
increased prostaglandins (?)
hyperplasia of JG apparatus (?)
resistance to exogenous angiotensin II infusion (?)
low serum Mg2+
low urinary Ca2+ excretion
What distinguishes hypokalemia caused by vomiting?
low chloride
