Potassium Flashcards
normal plasma K
3.5-5
handling of an acute K load vs acute K deprivation
handling of acute K load is quick: 75% of K load is taken up acutely into cells very quickly, followed by relatively reapid incr in renal K excretion (urinary K excretion can exceed filtered K load due to tubular K secretion); handling of K deprivation is slow (days to weeks) and therefore substantial K defecit can occur in meantime, also kidney cannot decr K excretion to the same level it decr Na excretion (minmum urine K is 5-15 mEq)
total body K vs plasma K
reduced TBK doesn’t affect plasma K as much as increased TBK does b/c cells can release K if plasma is deficient (but can’t take up K as easily); thus, if plasma is hypokalemic than the body must be severely TBK deprived
hormones that affect K
insulin, catecholamines, and aldosterone all send K into cells by incr Na/K pump activity (aldosterone also causes K excretion in kidney) and can be used to tx hyperkalemia and/or can cause side effects of hypokalemia (i.e. beta agonist side effect = hypokalemia)
factors affecting internal K balance (6)
plasma K concentration (high K stims Na/K pump and thus sends K into cells, high K in plasma also incr concen gradient for K to enter cells); hormones (insulin, catecholamines, aldo all send K into cells); exercise (K release from muscle); plasma tonicity (hypertonicity shrinks cells, thus incr. K concentration and creating a large concentration gradient for K to leave cells, also K leaves w/ water via solvent drag); acid-base balance (acidemia = hyperkalemia as H+ enters cells in return for K); cell lysis (rhabdomyolysis, hemolysis dump K into plasma)
hypertonicity effects on K balance (3)
hypertonicity shrinks cells, thus incr. K concentration and creating a large concentration gradient for K to leave cells, also K leaves w/ water via solvent drag –> hyperkalemia (incr by 1 mEq for each 20 mOsm incr) - most often seen w/ acute hyperglycemia (further impacted by lack of insulin in T1DM to send K back into cells)
glucose load effects on K in normals and diabetics
normal: glucose load induces insulin -> hypokalemia; diabetic: glucose load causes hypertonicity -> hyperkalemia
diabetics and K
glucose load in diabetes causes hyperkalemia b/c hypertonicity sends K out of cells and b/c insulin can’t send it back inside; however, kidneys in DKA tend to excrete K b/c ketoanions reach distal tubule and incr K excretion (more neg lumen) and b/c osmotic diuresis (glucose, ketones) -> may cause hypokalemia, particularly after hyperglycemia corrected w/ insulin; overall, diabetics have TBK deficit (loss in urine) but hyperkalemia in plasma (insulin lack, hypertonicity)
organic vs inorganic acidosis and K balance
organic acidosis (lactic acidosis, alcoholic ketosis, DKA) causes less hyperkalemia than inorganic acidosis (HCl, H2SO4, H3PO4), perhaps b/c organic acids enter cell as anion w/ H+ and thus K+ doesn’t need to leave
K reabsorption throughout kidney (%s)
prox nephron not regulated: 80% in PT, 10% in TAL; collecting duct regulated: in hyperkalemia, 20-180% can be secreted in initial collecting duct (20-40% will be reabsorbed again in CD despite hyperkalemia) -> total 10-150% filtered load excreted, vs. in hypokalemia, 2% will be reabsorbed in initial CD w/ 6% reabs in late CD -> total 2% filtered load excreted
K handling in PT (3)
in early prox tubule, reabs paracellularly due to solvent drag; in late tubule, small positive lumen V drives K reabs paracellularly; there is minimal secretion to lumen through luminal K channels
K handling in loop of Henle: thin descending limb, thin ascending limb, TAL
K passively secreted in thin descending limb (driven by high K permeability and high medullary K concentration); K passively reabs in thin ascending limb (this traps K in medullary interstitium -> incr capacity to secr K in distal tubule and CD during hyperkalemia); TAL reabs K both actively (accounts for 50%, via NK2Cl) and passively (accounts for 50%, due to positive lumen), some reabs K is secreted back into lumen through ROMPK while some exits the cell basolaterally
reabs and secretion of K in CD - what cells/channels are responsible?
principal cells secr K through aldo-sensitive channels and thru apical K-Cl synporter (driven by concentration gradient maintained by fast urine flow and by neg lumen V est by ENAC Na reabs); alpha IC cells reabs K through HK antiporter channels
reqs for K secretion into CD (3, lab values to get K secr)
aldo; Na delivery to CD (Na reabs through ENAC makes lumen negative and drives K secretion - need urine Na > 10-20 mEq/L to get K secretion); high urine flow rate (maintains concen. gradient; need urine V > 300-500 mL/day to get K secretion)
factors affecting distal nephron K secretion (4)
incr plasma K -> incr K excretion (independent of aldo); aldo -> incr K secretion; incr distal tubule Na delivery (-> neg lumen) and incr flow (maintain K concen gradient) -> incr K secretion; anions in tubular fluid (if NaCl delivered to tubule, Cl- absorbed relatively easily and tubule doesn’t get negative; if Na-sulfate delivered, sulfate is not as permeable as Cl- and thus is left behind -> more negative lumen = more K secr – we see this clinically w/ ketoanions, HCO3-, and anionic meds like penicillin)
non-reabsorbable anions: what do they do, what are they (4)
if NaCl delivered to tubule, Cl- absorbed relatively easily and tubule doesn’t get negative; if Na-sulfate delivered, sulfate is not as permeable as Cl- and thus is left behind -> more negative lumen = more K secr; we see this clinically w/ ketoanions, HCO3- (metabolic alkalosis kidney compensation, prox RTA), and anionic meds like penicillin or hippopurate (toluene, glue sniffing)
why doesn’t hypovolemia lead to hypokalemia via aldo?
hypovolemia -> RAAS -> AgII -> NaH in PT upregulated -> avid PT Na reabsorption -> low distal Na delivery -> no K secretion despite high aldo levels
hyperkalemia consequences (7)
cell swelling; cell alkalosis (K enters cells in exchange for H+); plasma acidosis (decr renal ammoniagenesis -> impaired urinary acidication); cell depolarization; muscle weakness and paralysis (initially incr muscle excitability followed by Na channel inactivation) which can lead to respiratory muscle failure; vasodilation (SMC relaxation); cardiac conduction disturbances and ventricular arrhythmias
hyperkalemia ECG
peaked T waves -> long PR w/ flattened p -> QRS wide -> sine wave (VF)
pseudohyperkalemia (4)
in vitro hemolysis assoc w/ leukocytosis (serum K high, plasma K normal), thrombocytosis (serum K high, plasma K normal), fist clenching during blood draw (exercise), fragile RBC in genetic disorders (hereditary spherocytosis)
dietary potassium (4)
potatoes, bananas, oranges, tomatoes
causes of hyperkalemia: 3 general classes w/ specifics
high K intake (us. needs impaired K excretion or internal K balance probs to cause hyperkalemia tho); impaired K excretion due to low GFR (AKI/CKD), RAAS probs (hypoaldo in Addison’s, type IV RTA, and meds; aldo resistance due to meds or tubulointerstitial CKD), inadeq distal tubule Na delivery and urine flow; abnormal internal balance due to insulin deficiency, hypertonicity, metabolic acidosis, drugs (beta antagonists, severe digoxin toxicity, succinylcholine), exercise, tissue damage/cell lysis
AKI effects on K balance (4)
causes hyperkalemia: decr distal Na delivery and urine flow; distal tubule dysfn prevents K secretion; tissue breakdown/catabolic state/metabolic acidosis lead to hyperkalemia; no adapative mechs to incr K secr in distal tubule and colon
CKD effects on K balance
can cause hyperkalemia, but only if GFR severely depressed (<15-20) b/c compensation occurs (distal nephron hypertrophy w/ incr. principle cell area, incr NK pump activity, and incr apical K channel activity; colon K secr incr.)
Addison’s: what is it, sx (4), dx (4), tx (2)
primary adrenal insufficiency: no aldo (hyponatremia in 90%, hyperkalemia in 65%, hypovolemia), no cortisol (fatigue, anorexia, weight loss); expect low aldo, low cortisol (blunted response to cosyntropin), high renin; tx w/ glucocorticoid and mineralocorticoid (fludrocortisone) - cortisol will help incr K excr by incr GFR and tubular flow
type IV RTA: aka (3), assoc w/ (5), pathogenesis (4), how does acidemia occur?
aka hyporeninemic hypoaldosteronism or hyperkalemic distal RTA or hyperkalemia hyperchloremic metabolic acidosis; most pts have both CKD and DM while some have chronic interstitial nephritis, SLE, and HIV; due to decr renin synthesis (80% pts), adrenal dysfn (decr aldo even w/ AgII administration, even though cortisol production is normal), V expansion (due to impaired GFR in CKD -> suppresses RAAS), decr renal response to aldo; decr aldo -> impaired distal tubule Na reabs and reduced NH4 synthesis (b/c hyperkalemia b/c no K secr) -> acidosis (decr H secr b/c no aldo, hyperkalemia, reduced ammonium synthesis)
hypokalemia in distal and proximal RTA due to (4)
variable K concentration (us a bit low) due to: mild hyperaldosteronism b/c Na lost w/ HCO3; incr distal nephron delivery of Na and HCO3 (poorly reabsorbable anion) stims K secr in CD; defect in HK ATPase in some distal RTAs (less K reabs); incr membrane K permeability in dRTA assoc. w/ amphotericin B
hyperkalemia and NH4 synthesis
hyperK causes reduced ammoniagenesis: hyperkalemia sends H+ out of cells in exchange for K+ into cells; cell perceives an alkaline intracellular environment and so wants to conserve acid and thus doesn’t generate ammonia for excretion –> thus, hyperkalemia causes acidemia by preventing bicarb production/ammonia excretion
vomiting effects on K balance
hypokalemia: Na lost in urine as NaHCO3 leads to hypovolemia -> hyperaldo -> K excretion in urine
what causes hypoaldosteronism? (3 classes)
Addison’s, meds (cyclosproine/tacrolimus, NSAIDs, B antagonists, ACEI/ARB, heparin), type IV RTA (decr renin synthesis, adrenal dysfn where aldo decr w/o cortisol decr, V expansion in CKD -> suppress RAAS)
meds that cause hyperkalemia (16)
hypoaldo caused by: cyclosproine/tacrolimus, NSAIDs, B antagonists, ACEI/ARB, heparin; decr aldo response: K sparing diuretics (triamerane/amiloride block ENaC, sprionolactone/eplerenone block aldo receptor), trimethorpim (antibx) and pentamide (anti P. carinii) block ENaC; abnormal internal K balance: beta antagonists, severe digoxin toxicity, succinylcholine
pseudohypoaldosteronism type 1: aka, mutation (2), renin/aldo levels, sx (4)
salt-wasting disorder of neonatal period; LOF mutation of ENac (AR) or aldo receptor (AD, sporadic); high renin and aldo (high aldo but low aldo effects due to receptor mutation) w/ severe Na wasting, hyperkalemia, V depletion, metabolic acidosis (sx of hypoaldosteronism)
pseudohypoaldosteronism type 2: aka (2), mutation (2), pathogenesis, renin/aldo levels, sx (2)
aka Gordons’ syndrome aka familial hyperkalemic hypertension (AD); incr. DCT NaCl transporter activity (due to WNK1/4 mutation) causes decr distal Na delivery and flow -> decr K secr -> hyperkalemia; normal GFR, low renin, low-normal aldo; sx: hypertension, hyperkalemia
TTKG: when to use, equation, values (3)
used as rough assessment of K secr in CD; transtubular K gradient = (Uk/Pk)/(Uosm/Posm); normally 7-10 (if low, then low K secr = hypoaldo or aldo resistance, if high, then high K secr = hyperaldo or hyperkalemia not due to hypoaldo); Uosm/Posm corrects for water reabs in CD that can impact Uk concentration
tx of severe acute hyperkalemia (3)
- antagonize cardiac effects w/ calcium gluconate (stabilizes membrane by incr threshold and incr # of Na channels, works w/in mins); 2. K redistribution into cells w/ insulin + glucose or w/ beta-2 agonist (albuterol -> avoid in pts w/ CHD) or w/ sodium bicarb (ineffective unless in setting of severe acidosis, may cause hypertonicity -> hyperkalemia worse); 3. K excretion w/ loop diuretics, Kayexalate (oral or enema), dialysis if v. severe
management of chronic hyperkalemic (6)
reduce intake, review meds, incr Na intake (NaCl, NaHCO3), loop diuretics, Kayexalate (oral or enema), fludrocortisone
causes of renal K wasting (7)
need both aldo and Na delivery: 1. diuretics or diuretic-like disease (Barrter’s/Gitelman’s) -> decr V (aldo incr) and block prox Na reabs (incr distal Na delivery); 2. vomiting -> decr V (causes incr aldo), incr NaHCO3 delivery to distal tubule (kidney attempting to fix alkalosis); 3. posthypercapneic alkalosis -> incr NaHCO3 delivery to fix alkalosis, this incr NaHCO3 loss means decr V (aldo incr); 4. primary hyperaldosteronism or apparent MC excess or glucocorticoid-remediable hyperaldo or hyperreninism or Liddle’s or CAH-> Na delivery incr b/c high ECF V therefore downregulation of proximal tubule Na reabs; 5. RTA -> incr Na in tubule due to RTA dysfn, incr aldo due to decr V due to Na wasting; 6. Hypomagnesemia -> Mg normally prevents K efflux thru ROMPK; 7. incr # non-reabsorbable anions in distal tubule (HCO3, ketones, penicillin, hippurate) -> distal lumen more negative -> K efflux
causes of hypokalemia (7 categories)
renal K loss: all diuretics, Bartter’s/Gitelman’s, vomiting, posthypercapneic alkalosis, RTA, hypomagnesemia, primary hyperaldo (or like it: apparent mineralocorticoid excess, CAH, hyperreninism, glucocorticoid-remediable hyperaldo, Liddles), incr # non-reabsorbable anions in distal tubule; incr K loss in stool (i.e. diarrhea); extreme sweat (K loss in sweat, also V loss -> hyperaldo); redistribution into ICF (only causes transient hypokalemia) due to drugs (beta 2 agonists and insulin) or alkalosis, rapid cell growth; inadeq. intake (rare, us. only modest hypokalemia unless assoc. renal excretion defect) due to “tea and toast” diet, anorexia, or alcoholism
diagnostic eval of hypokalemia
exclude transcellular shifts (transient hypoK), then measure Uk. If Uk < 20 mEq/day, then hypoK due to extrarenal loss (diarrhea, sweat). If Uk > 20/day, then hypoK due to renal losses. If normal BP, then look at serum bicarb. If serum bicarb low, then RTA. If serum bicarb high, then alkalosis. Look at urine Cl - if low (s, or CAH.
diseases like primary hyperaldosterinism (5)
apparent mineralocorticoid excess (cortisol can activate MR), CAH, hyperrenism (renal artery stenosis, renin-secr tumor, malignant HTN), Liddles (ENaC const. active), glucocorticoid-remediable hyperaldo (aldo responds to ACTH)
meds that cause hypokalemia (8)
cause redistribution into ICF: beta agonists, insulin; cause renal K loss: all diuretics other than K sparing diuretics; assoc w/ hypomagnesemia: diuretics, aminoglycosies, cisplantium, foscarnet, amphotericin B, alcohol
meds that cause hypomagnesemia (6)
diuretics, aminoglycosies, cisplantium, foscarnet, cyclosporine, amphotericin B, alcohol
causes of decr K intake (3)
tea and toast diet, anorexia, alcoholism (may cause hypokalemia due to decr K intake and due to magnesium depletion); however doesn’t us. cause hypokalemia b/c tissue breakdown releases K into ECF
causes of K shifts that lead to hypokalemia (6)
drugs: beta agonists (or endogeneous catecholamines), insulin (only drugs, not in insulinomas for some reason); alkalosis (altho hypoK in alkalosis is due to renal K wasting, not internal K shift); rapid cell growth (folic acid or B12 for megaloblastic anemia, parental hyperalimentation, granulocyte-macrophage colony stim factor for neutropenia); myeloid leukemia (pseudohypokalemia -> cells take up K from serum after blood draw); hypokalemic periodic paralysis
diarrhea presentation (3)
metabolic acidosis w/ normal urinary acidification and hypokalemia
causes of incr stool K loss (6)
diarrhea of any etiology; laxatives; villous adenoma (rare colonic tumor that secretes K); ureterosigmoidstomy (sigmoid colon changed into bladder, where it acts to secrete K and abs NaCl); Kayexelate; geophagia (ingestion of clay -> binds K)
sodium polystyrene sulfonate
Kayexelate -> resin binds K to facilitate excretion in GI tract
magnesium and K
magnesium depletion causes K wasting b/c Mg normally binds ROMPK preventing K efflux in TAL, w/o Mg K can leave cell -> tubule
pseudohypokalemia
myeloid leukemia -> cells takes up K from serum after blood draw
diuretics effect on K (4 classes and their effects)
loop/thiazide diuretic cause V depletion (-> aldo) and incr distal Na delivery (inhibit TAL/DCT Na reabs) -> incr K secretion -> hypokalemia, also cause alkalosis -> hypokalemia, thiazide are more kaliuretic b/c they have longer DOA and thus less likely to have K conserving time periods; acetazolamide causes V depletion (-> aldo) and incr distal Na delivery (w/ NaHCO3) and poorly resorbable anion (HCO3-) delivery -> hypokalemia; osmotic diuretics cause V depletion and incr distal NaCl delivery -> hypokalemia
primary hyperaldosteronism: sx (2, %), cause (2), dx
causes moderate to severe HTN (accounts for 1-2% of HTN pts); 60% due to adenoma, 40% due to bilateral adrenal hyperplasia; serum K may be normal in 40% pts (more commonly normal in bilateral adrenal hyperplasia) but rest have hypokalemia; dx w/ aldo/renin ratio (if > 20, then probably primary hyperaldo b/c aldo is high but renin is low due to neg feedback)
apparent mineralocorticoid excess
normally, cortisol is degraded in kidney by 11-beta-hydroxysteroid dehydrogenase-2; if this enzyme is deficient then cortisol can bind to MR and give sx of hyperaldo w/ low renin and aldo levels; enzyme can be mutated (causes severe juvenile HTN w/ hypokalemia and met. alkalosis), inhibited by licorice, or overwhelmed by high cortisol levels in Cushing’s due to ectopic ACTH
CAH
congenital adrenal hyperplasia can lead to excessive MC effect -> HTN, hypokalemia, alkalosis
hyperrenism etiologies (3)
renal artery stenosis, malignant HTN, renin-secreting tumors
glucocorticoid-remediable hyperaldosteronism
mutation combines cortisol enzyme and aldo enzyme, so that aldo synthesis is stimmed by ACTH and occurs in the zona fasciculata (normally cortisol producing tissue); administration of cortisol will shut off ACTH and decr aldo production; AD trait w/ HTN before 21 yo, hypoK in 50%, incr risk of hemorrhagic stroke (prob due to congenital HTN during cerebrovascular dev)
LIddle’s syndrome
AD disorder w/ early-onset HTN and hypokalemia but low renin and aldo; due to mutations in ENaC leading to constitutive activation; tx w/ amiloride but not spironolactone
amiloride
anti-ENaC
sprinonolactone
anti-MR receptor
Bartters vs Gitelman’s mutations
Think LAB TAG (loop barterrs thiazide gitelmans): Bartters in TAL -> NK3CL, CIC-Kb (basolateral Cl channel), ROMPK (apical K channel); Gitelman’s in DCT -> NaCl transporter
Barrters and Gitelman’s labs (6)
urinary Na wasting -> urinary K wasting, V depletion -> secondary hyperaldo and hyperrenin -> metabolic alkalosis; Barterr’s is hypercalcuiric (loss of positive lumen in TAL that allows Ca reabs) and can have nephrocalcinosis; Gitleman’s is hypocalcuric (enhanced reabs in DCT due to impaired transport of NaCl -> hyperpolarization)
hypokalemia on EKG
ST depression and T flattening, prominent U wave (after T)
hypokalemia consequences: cardiac (1), neuromuscular (4), endocrine (4), renal (5)
cardiac: ventricular arrhythmias (incr risk for digitalis toxicity); neuromuscular: constipation, weakness, paralysis (us. peripheral but not respiratory muscles), rhabdomyolysis; endocrine: decr aldo, incr renin (b/c decr RBF, altho Na retention counteracts), incr renal prostaglanin synthesis, decr insulin (mild glucose intolerance -> worsens hyperglycemia in diabetics); renal: polyuria and polydipsia (nephrogenic DI due to downregulation of aquaporin-2), incr ammoniagenesis (can lead to hepatic coma in pts w/ decr liver fn that can’t break down ammonia), met. alkalosis, Na retention (-> HTN), chronic interstitial nephritis
hypokalemia tx
tx not emergency unless arrhythmias or profound weakness; prefer to use oral K to minimize hyperK risk: high K foods in mild hypokalemia, oral K preps in moderate hypoK; if rapid correction needed, use KCl (esp in metabolic alkalosis) or K citrate/K acetate if metabolic acidosis (diarrhea, RTA) – avoid IV K unless absolutely neccesary, and check K often!
