Relative % of potassium inside cells vs in the EC fluid
98% inside cells vs 2% in EC fluid
Relative % of dietary potassium excreted in urine vs eliminated in stool
90% in urine vs 10% in stool
How is potassium handled in the nephron?
1. Freely filtered but quickly reabsorbed in the PCT and loop of Henle. Relatively stable.
2. Variable amount of K is secreted from the cortical collecting duct-->determines amount of K excreted
2 mechanisms by which K is secreted
1. Transcellular via basolateral Na/K ATPase and luminal K channel
2. Paracellular driven by voltage of -50 mV compared to blood 0 mV
What 4 variables determine K secretion in the distal nephron?
1. Cellular K concentration (greater-->more secretion)
2. Luminal K concentration (smaller-->more secretion)
3. Voltage across luminal membrane (more negative-->more secretion; also increases paracellular secretion)
4. Permeability of luminal membrane to K
2 major regulators of aldosterone release
4 effects of aldosterone on cortical collecting duct
1. Increases Na absorption through the luminal channel (makes voltage more negative-->increase K secretion)
2. Increases K secretion through the Na/K pump (increases cellular K concentration)
3. Increases H secretion through intercalated cells in the collecting duct
4. Increases K permeability through luminal membrane
Besides aldosterone, what other physiologic factor influences potassium secretion? Three reasons for this phenomenon
Increased sodium/water delivery to the cortical collecting duct; this increases potassium secretion b/c it
1. increases sodium reabsorption which makes the voltage more negative, favoring K secretion
2. increases activity of the Na/K ATPase, which increases K concentration in the cell, favoring potassium secretion
3. dilutes the apparent concentration of K in the lumen, favoring K secretion
How do nonreabsorbable anions affect potassium secretion? Two reasons for this influence
They favor potassium secretion by:
1. increasing Na/volume delivery to distal nephron
2. making distal nephron luminal voltage more negative
How is potassium homeostasis maintained in volume-overloaded and volume-contracted states?
When pts are volume-overloaded,
1. increased distal Na delivery stimulates K secretion
2. decreased aldosterone lowers K secretion
When pts are volume-contracted
1. decreased distal Na delivery lowers K secretion
2. increased aldosterone stimulates K secretion
Therefore, K secretion is independent of volume status
4 general abnormalities affecting K excretion
1. primary mineralcorticoid excess--e.g. aldosterone secreting tumor; leads to hypokalemia
2. primary increase in distal delivery of Na--e.g. diuretic; leads to hypokalemia
3. primary decrease in mineralcorticoid--e.g. Addison's dz; leads to hyperkalemia
4. primary decrease in distal delivery of Na--e.g. ARF; leads to hyperkalemia
3 physiologic determinants of K uptake into cells
1. plasma K: as it rises, uptake increases directly
2. insulin: hyperkalemia stimulates insulin release, which stimulates K uptake in liver and skeletal muscle cells (prevents postprandial hyperkalemia)
3. epi: hyperkalemia stimulates epi release, which stimulates beta-2 receptors on liver and muscle cells to uptake K (prevents hyperkalemia during exercise)
5 pathologic determinants of K uptake into cells
1. acid/base disorders
2. cell death
5. periodic paralysis
4 general categories of causes of hypokalemia
1. decreased uptake--rare; usually malnutrition
2. GI loss (diarrhea)
3. renal loss
4. cellular redistribution
Difference b/w changes in excretion of sodium and potassium in times of decreased intake
1. Sodium--if stop eating Na, urinary and fecal excretion of Na will go to zero
2. Potassium--if stop eating K, urinary and fecal excretion of K won't fall down to below 5 mEq/day and 10-15 mEq/day respectively
Therefore, easier to develop dietary hypokalemia than dietary hyponatremia
How does vomiting cause hypokalemia?
Not a true gastric loss of potassium; rather, vomiting causes a metabolic alkalosis which leads to renal K wasting b/c to correct the alkalosis the kidney does not reabsorb bicarb. Bicarb turns into a nonreabsorbable anion, which increases K secretion
Also, alkalosis leads to redistribution of K into cells, worsening the hypokalemia
How does diarrhea cause hypokalemia?
True potassium wasting
Diarrhea causes metabolic acidosis, which causes K to redistribute out of cells, causing a hypokalemia that is not as severe as the degree of K wasting
3 categories of hormone excess causing hypokalemia
1. primary aldosteronism: e.g. Conn's dz (benign tumor of zona glomerulosa) or bilateral adrenal hyperplasia. Low renin, high aldosterone
2. excess renin production e.g renin-secreting tumors, renovascular HTN, accelerated HTN. High renin, high aldosterone.
3. excess cortisol-->: e.g. Cushing's syndrome; the mineralcorticoid effect of a glucocorticoid (therefore less severe hypokalemia than found in say Conn's dz). Low renin, low aldosterone.
Besides physically taking a diuretic, what else can cause increased distal delivery and hypokalemia?
osmotic diuresis e.g. in poorly controlled DM
3 examples of nonreabsorbable anions causing hypokalemia
1. carbenicillin (and certain other penicillins)
2. ketoacids (DM, starvation, alcoholism)
3. bicarb (if delivered to distal nephron in greater quantities than can be absorbed e.g. in alkalosis, proximal renal tubular acidosis, and acetazolamide)
2 examples of cellular redistribution causing hypokalemia
1. alkalosis (causes K to shift into cells)
2. hypokalemic periodic paralysis: "channelopathy" in which K periodically redistributes inside the cell
How do you determine whether pt has GI loss or renal loss in hypokalemia?
Do they have diarrhea? Do they abuse laxatives? If unsure, measure 24 hr urinary potassium. If below 20 mEq/24 hr, then GI loss (assuming normal kidney function). If greater than 20 mEq/24 hr, then renal loss.
How do you determine whether renal loss of K is due to primary increase in distal delivery or primary increase in mineralcorticoids?
Assess volume status
Volume depletion is associated with increased delivery
Volume expansion/HTN is associated with increased mineralcorticoids
If pt has primary increase in mineralcorticoid activity, what tests should you order?
plasma renin and plasma aldosterone levels
3 general categories of causes of hyperkalemia
1. increased intake
2. decreased renal excretion (decreased delivery, decreased mineralcorticoid, distal tubular defect)
3. cellular redistribution
What are 6 causes of cellular redistribution resulting in hyperkalmiea?
1. cell death/ischemia
5. hyperkalemic periodic paralysis
6. insulin deficiency
What are three causes of pseudohyperkalemia?
1. marked thrombocytosis
2. marked leukocytosis
3. hemolysis of blood sample
How to confirm pseudohyperkalemia
re-measuring serum K in a heparinized sample tube.
What determines whether in AKI you develop hyperkalemia?
Whether there is oliguria present. Usually when the AKI is non-oliguric, there is enough distal delivery to prevent hyperkalemia
What three adaptations occur in CKD to prevent hyperkalemia?
1. remaining nephrons adapt and increase ability to excrete potassium.
2. redistribute potassium into cells faster
3. increase stool excretion of potassium
Below what GFR is associated with hyperkalemia due to CKD?
less than 5 cc/min
Hyperkalemia + GFR > 10 cc/min indicates what two possible disease processes?
1. decreased mineralcorticoid
2. specific lesion in the cortical collecting duct
Two categories of hypoaldosteronism
1. isolated hypoaldosteronism: e.g. hyporeninemic hypoaldosteronism
2. combined hypocortisolism and hypoaldosteronism e.g. Addison's dz
Pathophysiology of hyporeninemic hypoaldosteronism
In CKD (e.g. interstitial nephritis, diabetic nephropathy), renal insufficiency leads to decreased renal production from kidney resulting in decreased aldosterone production
Two examples of non-diuretic drugs affecting aldosterone synthesis and causing hypokalemia
ACE-I: leads to decreases A-II and aldosterone-->hypokalemia
Heparain: can inhibit aldosterone synthesis
What diuretics raise the risk of hyperkalemia in patients with chronic renal insufficiency or diabetic nephropathy?
Amiloride, triamterene, spironolactone
Most important cause of cellular redistribution resulting in hyperkalemia
tissue damge--rhabdomyolysis, burns, trauma, tumor lysis, DIC
Common cause of hyperosmolarity resulting in hyperkalemia
DM--rise in blood glucose
Category of drugs causing hyperkalemia via depolarization
anesthetics e.g. succinylocholine. Deploarizing cell membranes causes K to leave cells
Which causes potassium to shift out of cells--administering an organic acid or inorganic acid?
Mechanism of hyperkalemia in ketoacidosis and lactic acidosis
NOT primary due to organic acid in blood
rather, in ketoacidosis is due to hyperosmolarity and decreased insulin; and in lactic acidosis is due to cell ischemia
Clinical categories of hyperkalemia
1. "office" hyperkalemia--asymptomatic, coincidental finding on routine blood test; due to abnormal CCD or primary decrease in mineralcorticoid.
2. "ICU" hyperkalemia--extremely ill; due to cell shift or kidney injury
Clinical manifestations of hypokalemia
1. NM: hyperpolarization-->flaccid paralysis moving from extremities to trunk to diaphragm
2. frank rhabdomyolysis
3. smooth muscle dysfunction e.g. paralytic ileus
4. ST depressions, T wave flattening, increased U wave-->PVCs, SVT, V tach
5. interstitial nephritis (due to decrease in medullary gradient and CCT resistance to ADH)
6. nephrogenic diabetes insipidus (due to hypernatremia)
7. glucose intolerance
Clinical manifestations of hyperkalemia
"depolarization block" and slowed conduction velocity
1. cardiac: peaked T wave-->widened QRS and PR interval-->P wave disappears-->QRS and T wave form a "sin wave"-->cardiac standstill
2. NM: paresthesia in extremities, followed by symmetric flaccid paralysis beginning in hands and feet and moving proximally; spares the head, trunk, and respiratory muscles