P OTASSIUM BY; Dr BASHARDOUST

P OTASSIUM Control of normal K + homeostasis Hypokalaemia Hyperkalaemia

[Na + ] = 20 [K + ] = 150 [K + ] = 4 [Na + ] = 140 K + gradient across cell membranes sets cell voltage (Na + gradient can be usefully linked to solute transport)

Regulation of K + balance Normal dietary intake: mmol/day 3 components to maintain (‘defend’) homeostasis:  Cell shifts  Renal excretion  GI loss (weak and poorly regulated)

K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ 90%K + Renal K + handling K+K+ (CCD) (PT) (LOH)

2K + 3Na + K+K+ K+K+ Na + 3Na + 2K + Principal cell Cortical collecting duct (CCD) Amiloride Barium Ouabain -70mV LumenBlood

Cell shifts 2% of total body K + in ECF = ~50 mmol/l (= a good steak meal!) - insulin (Na +,K + -ATPase) – goes up when you eat - sympathetic -  2 (uptake) vs.  (brake) (*insulin has as much to do with K + homeostasis as with glucose) So ‘defence’ needed to prevent hyperkalaemia:

What determines CCD K + secretion? Mineralocorticoid activity Distal delivery of Na + (and flow rate) - nonreabsorbable(NR) anions, e.g. HCO 3 -

2K + 3Na + K+K+ K+K+ Na + 3Na + 2K + Principal cell Control of CCD K + secretion -70mV Distal delivery of Na + Mineralo- corticoids K+K+ LumenBlood

K + secretion in CCD AldosteroneDistal Na + delivery K + secretion  ECV     ECV     Conn’s (ECV  )     Diuretics (ECV  )   Addison’s (ECV  )     (CCD)

H YPOKALEMIA Hypokalemia is defined as a serum potassium concentration less than 3.5 meq/L (3.5 mmol/L). The serum potassium concentration may be a misleading marker of the degree of a patient’s serum potassium deficit, as patients with normal or even increased serum concentrations of potassium may have significant total body potassium depletion. The exact cause of hypokalemia can usually be established by evaluating the history, blood pressure, acid-base balance, and urine potassium concentration

Hypokalaemia Pseudo- (leukaemia, but only at room temp) Cell shifts Dietary intake (not usually a problem unless another source of K + loss, e.g. diarrhoea or malabsorption) GI loss Renal loss

Hypokalaemia - cell shifts  Alkalosis - minor  Barium toxicity – remember CCD principal cell  Rapid cell growth - anabolism  Hypokalaemic periodic paralysis – Ca 2+ channel mutation (presents at years of age)  Thyrotoxicosis – Asian males

Extrarenal K + loss Bowel K + loss Diarrhoea is the most common cause Urinary K + excretion is typically <20 mmol/day Renal K + loss Vomiting-associated hypokalaemia

Renal K + loss Diagnosis -Urinary K + excretion >20 mmol/day -No diarrhoea (but remember to consider laxative abuse)  A primary  in mineralocorticoidversus  A primary  in distal Na + delivery - ECV expansion - BP elevation

A primary increase in mineralocorticoid  Primary hyper-reninism – renin and aldosterone  (not corrected by i.v. saline) - Malignant hypertension (~50%) -Renal artery stenosis (~15%) - Renin secreting tumour  Primary hyperaldosteronism – renin  - Conn’s syndrome (adrenal adenoma) - Bilateral adrenal hyperplasia - GRA (glucocorticoid remediable aldosteronism)  Primary increase in a non-aldosterone mineralocorticoid – renin and aldosterone  - Cushing’s syndrome - CAH (congenital adrenal hyperplasia) - AME (apparent mineralocorticoid excess) - Liddle’s syndrome

A primary increase in distal Na + delivery - Diuretics that act upstream of the CCD - Nonreabsorbed anions - Mg 2+ deficiency - Bartter’s syndrome - Gitelman’s syndrome - Acidosis

Na + 2Cl - Cl - K+K+ H+H+ URINE 3Na + 2K + Proximal tubule Thick ascending limb Distal tubule Collecting duct Na + transport along the nephron CELL - Osmotic diuretics - CA inhibitors - Loop diuretics - Bartter’s - Thiazides - Gitelman’s - Triamterene - Amiloride - Spironolactone

Nonreabsorbed(NR) anions Failure to reabsorb in the proximal leads to an increase distal Na + delivery Failure to reabsorb in the CCD leads to increased cation (K + or H + ) secretion in ‘exchange’ for Na + (absorption) Examples: - HCO 3 - (Urine pH high) - keto-anions (DKA) - penicillins

Mg 2+ deficiency/Metabolic acidosis Mg 2+ deficiency inhibits TAL Na + absorption - hypokalaemia, alkalosis, hypocalcaemia Acidosis inhibits proximal tubule Na + reabsorption  -  urinary K + loss in diarrhoea Bicarbonaturia in proximal RTA causes urinary K + loss Hypokalaemia occurs in distal RTA

HYPOKALAEMIA - an algorithm  U K  or  <20 mmol/day>20 mmol/day Renin, aldosteronePlasma [HCO 3 - ] BP, ECV High Low/Normal RAS Conn’s/adrenal hyperplasia GRA Cushing’s AME Liddle’s Low High RTA Urine [Cl - ] LowHigh Gastric NR anion Diuretics Mg 2+ deficiency Bartter’s Gitelman’s Diarrhoea

Risks of hypokalaemia PKPK ‘Bad’ events Post-MI Hypokalaemia in this setting may be due to high adrenaline BUT high adrenaline is a marker of poor outcome post-MI

Treatment of hypokalaemia Chronic - KCl liquid or Slow K - deficit will be at least 100 mmol Acute - i.v. KCl (no more than 20 mmol/h) If hypokalaemic and acidotic - treat hypokalaemia first!

Hyperkalaemia Pseudo- (high wbc, platelet counts and leaky rbc, but check that ECG is normal!) Excess K + intake Cell shifts Renal retention (sustained hyperkalaemia)

PERKALAEMIA

P SEUDOHYPERKALAEMIA High K + with a normal ECG, think of: o Repeated fist clenching o Haemolysis from a small gauge needle o Sample stored on ice and/or delayed transfer (causing efflux from red cells) o Hyperventilation o Release from leukaemic cells o Interference with K + -ion sensitive electrode from benzalkonium (topical antiseptic) or heparin o Familial (chromosome 16)

Cell shifts Cell damage - rhabdomyolysis, haemolysis, tumour lysis Diabetic ketoacidosis, nonketotic hyperosmolar Lactic acidosis Toxins and drugs - digoxin, tetrodotoxin* *Hyperkalaemic periodic paralysis

Acidosis and K + shifts INORGANIC acids do cause K + to leave cells (H + influx and buffering) ORGANIC acids do not cause K + to leave cells In DKA K + exit from cells is due to lack of insulin Hyperosmolarity also shrinks cells and the gradient for K + exit (loss) from cells In lactic acidosis - cell ischaemia, ATP  leads to K + leak out of cells Asymptomatic hyperkalaemia - think of a renal cause

Renal retention of K + Primary decrease in mineralocorticoid - hyporeninaemic hypoaldosteronism (DM, cID) - heparin - Addison’s Primary decrease in distal delivery of Na + - oliguric ARF (cf. non-oliguric) - acute GN - Gordon’s syndrome (pseudohypoaldosteronism type II) Abnormal CCD function - pseudohypoaldosteronism type Ia (ENaC) or Ib (MR) - cID (destroys CCD) - obstruction - amiloride, trimethoprim, pentamidine - spironolactone

Treatment of hyperkalaemia Acute - CaCl 2 - NaHCO 3 /glucose+insulin/b 2 agonists - Ca 2+ resonium/dialysis Chronic (assess aldosterone/ECV) - if low give fludrocortisone - if high (  BP) give diuretic - NaHCO 3 useful in all patients - low K + diet - Ca 2+ resonium (beware, may actually  K + acutely!) (slow!)