#2 - Disorders of Fluid and Potassium Flashcards
Normal K+ concentration
3.5-5.3 mEq/L
K+ distribution in body
98% in cells, 2% ECF
K+ excretion
90% in urine, 10% in stool
GI excretion can increase in kidney failure to 50%
K+ is reabsorbed by proximal tubule but
secreted by cortical collecting duct - rate of secretion determines K+ excretion rate
K crosses collecting duct in 2 ways
Transcellular > paracellular
- Transcellular route - Na/K-ATPase on basolateral side makes high intracellular concentration, then diffuses along gradient into lumen which is less negative but conc. gradient favors it
Rate of transcellular K secretion =
rate of K diffusion across luminal membrane
Increased by:
- Increased intracellular [K], permeability of luminal membrane to K, decreased luminal [K], and more negative lumen
Insulin and B2-adrenergic stimulation both
shift K+ into cells, insulin after eating and B2/epinephrine during exercise
Mineralocorticoid - Aldosterone
Secreted from zona glomerulosa of adrenal cortex in response to hyperkalemia and Ang. II
- Increases rate of Na+ absorption through luminal channel (makes lumen more negative)
- Increases K+ secretion through Na/K pump
- Increase K+ permeability of luminal membrane
- Increases H+ secretion by intercalated cell
Decreased EABV normally causes
- Increased aldosterone from increased JG, renin, AII activity
- Decreased distal Na+ delivery due to increased proximal absorption
Increased EABV normally causes
- Decreased aldosterone from decreased JG activity
- Increased distal Na delivery from decreased proximal absorption
Distal delivery of Na and H2O are
correlated together
- Increased delivery of Na stimulates distal Na absorption which makes lumen more negative and increases K secretion, also making Na/K pump work faster
- Higher flow rates also remove positive charges in lumen more so more K can be secreted
Non-reabsorbable anions effect on Na and volume
increase distal Na delivery because coupled with it, secondarily increasing K secretion, also making lumen more negative. More poorly reabsorbable anions will increase it more.
Primary mineralocorticoid excess
E.g. aldosterone secreting tumor, primary aldosteronism - benign tumor of zona glomerulosa = Conn’s syndrome
- Increased aldosterone activity and distal delivery causes K+ loss and hypokalemia
Primary increase in distal delivery
E.g. diuretics
- Increase distal delivery and Na loss with volume depletion and increased aldosterone causing K loss and hypokalemia
Primary decrease in mineralocorticoid activity or distal Na delivery
Seen in destruction of adrenal gland, acute renal failure
- Cause decreased distal delivery and aldosterone causing K+ retention and hyperkalemia
Hyperkalemia stimulates
cell K+ uptake directly, and also through hormones such as insulin and epinephrine
Hypokalemia disorder causes
inadequate intake, GI loss, renal loss, cellular redistribution
Hypokalemia from inadequate dietary intake because
some K always lost, unlike Na which can go to virtually zero excretion if necessary
2 Most common causes of hypokalemia
- Diarrhea - fecal K+ wasting and acidosis causes K+ out of cells which partially helps
- Vomiting - greater K+ depletion, not from gastric loss but metabolic alkalosis which causes kidney to not reabsorb HCO3-, causing K+ wasting. Alkalosis also causes redistribution of K into cells worsening the hypokalemia
- Urinary K+ < 20 mEq
Acidosis and alkalosis cause K+ to redistribute
out of and into cells, respectively
Hypokalemic periodic paralysis
intermittent attacks of muscle weakness triggered by large carb meals (insulin) or rest post-exercise (epinephrine) where K+ gets acutely shifted into cells
- Inherited form - dominant a-1 mutation in Ca channel
- Acquired - hyperthyroidism
Conn’s Syndrome
benign tumor of zone glomerulosa - produces excess aldosterone in absence of volume contraction > K+ loss and hypokalemia
- resolves if tumor removed
Bilateral adrenal hyperplasia
HTN will not respond even to bilateral removal
Primary aldosteronism
conditions where excess aldosterone secretion is cause of primary adrenal disease, e.g. Conn’s Syndrome and bilateral adrenal hyperplasia
Cushing’s syndrome
elevated cortisol and increased secretion of deoxycorticosterone and corticosterone B which have intermediate mineralocorticoid activity, causing milder hypokalemia
High renin and aldosterone points to
primary hyperreninemia such as renal artery stenosis or renin secreting tumor
Low renin and high aldosterone points to
primary hyperaldosteronism, such as adrenal adenoma, bilateral adrenal hyperplasia, glucocorticoid suppressible hyperaldosteronism, Conn’s syndrome - aldosterone-secreting tumor
Low renin and low aldosterone points to
increased level of non-aldosterone mineralocorticoid such as Cushing’s, 11 B or 17 a-hydroxylase deficiency, Liddle Syndrome
Ectopic ACTH secreting tumors cause
very severe hypokalemia
Glucocorticoid suppressible hyperaldosteronism
dominant disease forming chimeric protein joining ACTH response element with coding region of ADH synthase
Syndrome of apparent mineralocorticoid excess
Can be genetic or acquired - e.g. Cushing’s or licorice/chewing tobacco which have Glycerrhetinic acid which inactivates 11B-hydroxylase which forms cortisol from cortisone
Liddle Syndrome
Low renin and aldosterone, no response to inhibitor of aldo secretion or spironolactone
- Due to ENaC mutation that prevents its ubiquitination and degradation, leading to excessive Na reabsorption
Triamterene normalizes BP and K (also renal transplant)
Diuretic ingestion can cause hypokalemia through
increased distal NaCl delivery and increased aldosterone levels for acetazolamide or thiazides which work proximal to CCD
Bartter’s Syndrome
primary defect in loop of Henle salt absorption, causing increased distal delivery and hypokalemia with high renin and aldosterone
Gitelman’s Syndrome
defect in distal convoluted tubule NaCl absorption, causing hypokalemia with high renin and aldosterone
Nonreabsorbed anions can increase distal Na delivery and cause hypokalemia
HCO3-, ketoanions, Penicillins, hippurate (glue sniffing), salicylate (aspirin overdose)
Vomiting primarily causes hypokalemia through
alkalosis > HCO3- excretion which increases NaHCO3 delivery and K excretion, with low Cl-
Hypokalemia not due to renal dysfunction should not excrete more than
20 mEq of K per 24 hr
Pseudohyperkalemia
errors in processing samples due to K release from thrombocytosis or leukocytosis; can confirm by re-drawing blood in heparinized tube
Hyperkalemia caused by decreased renal excretion from
abnormal CCD function, decreased mineralocorticoid levels or distal salt delivery
Chronic kidney disease adaptations
remaining nephrons more effective at excreting K, K can redistribute to cells faster and they can excrete more in stool
Addison’s disease
aldosterone and cortisol deficiency due to destruction of adrenal glands
ACE inhibitors and heparin decrease
synthesis of aldosterone synthesis which can cause hyperkalemia
Hyporeninemic hypoaldosteronism
occurs in chronic kidney disease, diabetic nephropathy, interstitial kidney disease - renin and aldosterone both low due to decreased renin production by kidney
Amiloride and triamterene inhibit
Na transport making lumen more positive and causing hyperkalemia
Spironolactone
competes with aldosterone and blocks its effect, weakening defense against hyperkalemia
Cellular redistribution more important as a cause of
hyperkalemia, especially from tissue damage which releases K from cells, rhabdomyolysis, burns, diabetics with high glucose levels, and depolarizing anesthetics such as succinylcholine
Inorganic acid causes
K out of cells; organic acid does not cause a shift, so ketoacidosis and lactic acidosis K shifts out of cells are due to hyperosmolarity and insulin deficiency and cell ischemia
Hypokalemia effects
- Neuromuscular - weakness and flaccid paralysis, rhabdomyolysis
- Cardiac arrhythmias
- Concentration defects and metabolic alkalosis; resistance to ADH > polyuria and polydipsia
- Glucose intolerance
Hyperkalemia effects
Cardiac arrest
Neuromuscular - paresthesias leading to paralysis
Cardiac complications of hypokalemia
ST depression, T wave flattening, increased U wave
Cardiac complications of hyperkalemia
Causes depolarization block, peaked T wave > QRS and PR widening > “sin wave” of merged QRS and T waves > systole and death
Treatment of acute hyperkalemia
- CaCl - blocks effect of K+ on heart
- NaHCO3, glucose, insulin, B2 agonists - shift K into cells
- kayexelate, dialysis - remove K from body
Treatment of hypokalemia
address underlying cause
- Chronic - KCl liquid or slow
- Acute - IV KCl
- If hypokalemia accompanied by acidosis, treat hypokalemia first because it must be very severe as acidosis normally shifts K out of cells
