Potassium Disorders

Question 1

Clinical manifestations

Answer 1

Normal range 3.5-5.1 mol/L
- ICF/ECF K affects electrical potential and hence the membrane excitability of neuromuscular organs, muscles and heart

HyperK

• depolarise membrane and inactivate Na –> decrease excitability
• risk of arrhythmia

HypoK

• remove Na channel inactivation –> more depolarisation and increase excitability
• muscle weakness, paralysis

Question 2

Potassium homeostasis

Answer 2

Intake
Transcellular shift (Na/K pump - insulin/ catecholamines/ thyroxine, pH - H in/K out)
Extra-renal excretion e.g. sweat, faeces
Renal excretion
- passive secretion by tubular cell at CCD
- enhanced by flow rate, aldosterone (increase K channels and Na/K pumps – net increase Na reabsorption at expense of K and H)

Question 3

Approach to HyperK

Answer 3

1. Rule out pseudohyperK (very common)
2. Assess patient
3. DDx of hyperK (often multifactorial)

Question 4

Cause of PseudohyperK

Answer 4

1. Exogenous contamination during blood taking
   - EDTA (purple) and fluoride (grey)
   - both containing K salts; fluoride has K-oxalate or K-EDTA
   –> EDTA and oxalate irreversibly bind Ca and Mg and inhibit ALP activity
   ==> high K, low Ca/Mg, low ALP
2. Drip arms
   - dextrose drip with K supplement = all analytes diluted except K
   - NS with K = Na normal
   —> check patient status and presence of drip, check other bloods drawn at the same time for any dilution e.g. Low Hct
3. Ex vivo release from cells (high K, PO4, AST, ALT, ALP, LDH)
   - haemolysis/ traumatic venipuncture/ prolonged tourniquet
   - overnight sample (cell lysis, loss of Na/K pump)
   - chilled sample (cold inhibition of Na/K pump)
   - thrombocytosis, leukocytosis (fragile cells)

Question 5

Remember order of draw!

Answer 5

Blood culture –> Blue (Na citrate) –> Red (Serum) –> Green (Li Heparin) –> Purple (K3EDTA) –> Grey (NaF/ KOx)

Question 6

Causes of true HyperK: intake

Answer 6

Increased intake

• contributing factor but rarely sole cause
  e. g. K-containing IV fluids, massive GI bleed, transfusions, foods (citrus fruits, bananas, broccoli etc)

Question 7

Causes of true HyperK: transcellular shift

Answer 7

K shift out as buffer:

• acidosis with minerals i.e. HCl (Not lactic/keto/resp acidosis! – able to enter cell and balance H+ charge)
• hypertonicity

Cell lysis:

• tumour lysis syndrome after chemotherapy –> hyperK, hyperUr, hyperPO4, hypoCa
• rhabodomyolysis –> hyperK, hyperUr, hyperPO4, hypoCa, increase CK, myoglobinuria
• burns, trauma

Na/K ATPase activity decreases

• decrease SNS e.g. beta blockers, alpha agonists
• decrease insulin e.g. DKA, familial hyperK periodic paralysis
• drugs e.g. digoxin

K channel more open (less common)
- drugs: succinylcholine

Question 8

Causes of true HyperK: decreased excretion

Answer 8

GFR <10-15 ml/min
- ARF, CRF

GFR >10-15 ml/min

• hyperK uncommon in CKD until GFR <15
• low effective circulating volume (K secretion depends on flow) e.g. HF, liver failure
• if r/o above, consider mineralocorticoid deficiency (TTKG)

Drugs:
Decrease flow/ Na delivery
- NSAID (less vasodilation of afferent)
- beta blockers (less vasoconstriction of efferent)
- amiloride (block ENaC)

Decrease RAAS

• aldosterone antag e.g. spironolactone
• ACEi/ ARB
• direct renin inhibitors

Question 9

Trans-tubular potassium gradient (TTKG)

Answer 9

Estimates tubular conc. of K at CCT

• surrogate marker of mineralocorticoid activity
• normalised by urine:plasma Osm
• only valid if Uosm >300 and UNa >25

U[K]/Uosm // S[K]/Sosm

Normal = 6-8

TTKG >10 = not suggestive of mineralocorticoid insufficiency
TTKG <6 = insufficienct activity

Question 10

Causes of true hyperK: further differentiation of TTKG <6

Answer 10

Low renin - low aldosterone = renin insufficiency
- hyporeninemic hypoaldosteronism

High renin - low aldosterone = aldosterone insufficiency

• adrenal insufficiency
• congenital adrenal hyperplasia

High renin - high aldosterone = aldosterone resistance
- tubular disorders e.g. SLE, amyloidosis, obstructive uropathy

Question 11

Acute management of hyperK (>6 mmol/L or ECG changes)

Answer 11

Stop all K supplements, NSAIDS, ACEi, K sparing diuretics (aldo antag, ENaC blocker), Digoxin, Succinylcholine

Stabilise membrane:
- *10% Ca gluconate (increase excitability threshold)

Intracellular shift:

• *Dextrose-insulin drip
• IV bicarbonate
• beta agonist

Excretion:

• *resonium C (binds to K in GI system)
• furosemide (if renal failure)

Find and treat underlying cause

Question 12

Approach to HypoK

Answer 12

1. Rule out pseudohypoK (rare)
   - marked leukocytosis kept at room temp for long time (alive and uptake K)
2. Assess patient
3. DDx of HypoK (intake, shift, excretion; acid-base status and BP)

Question 13

Causes of hypoK: intake

Answer 13

Decreased intake fairly common

• anorexia
• alcoholism
• dementia

Question 14

Cause of hypoK: transcellular shift

Answer 14

Increase Na/K ATPase activity

• increase SNS e.g. stress, beta-2 agonist, theophylline, thyrotoxic hypoK periodic paralysis
• increase insulin e.g. iatrogenic, hypoK periodic paralysis

K shift as buffer
-metabolic alkalosis

Question 15

Periodic paralysis

Answer 15

Muscle channelopathy, usually AD inheritance
Transient episodes of paralysis due to transcellular shift of K

HyperK periodic paralysis

• infancy/ early childhood
• cold, rest after exercise, ingestion of small amounts of potassium

HypoK periodic paralysis

• men, late childhood/ teenage
• ppt by release of catecholamines/ insulin e.g. rest after exercise, high carb meal
• increase Na/K ATPase activity –> intracellular K shift with defective K efflux –> hyperpolarise membrane
• avg K during attack is 2.4 mmol/L

Thyrotoxic hypoK periodic paralysis

• men
• 2% asians with hyperthyroidism
• like hypoK paralysis but a/w hyperthyroidism (increases adrenergic responses)

Tx: K supplement, propanolol, definitive anti-thyroid treatment

Question 16

Causes of hypoK: excretion - non-renal

Answer 16

Non-renal loss

• U[K] <20 (not very reliable, easier to diagnose clinically)
• GI e.g. diarrhoea, laxative, villous adenoma (excrete HCO3) –> HCO3 loss and metabolic acidosis
• GI e.g. villous adenoma (excrete Cl) –> metabolic alkalosis
• sweat

Question 17

Causes of hypoK: excretion - renal, normal BP

Answer 17

U[K] >20 + NORMAL BP

• metabolic alkalosis and U[Cl] <10 = losing HCl via non-renal
• -> Vomiting/ NG tube aspiration
• Cl loss –> increase plasma HCO3 –> stays in tubular lumen and retain Na/H20 –> increase flow and Na delivery at CCD –> increase K secretion
• Maintained by volume depletion –> activate RAAS –> exaggerate hypoK and alkalosis (paradoxical acuduria)

Treat with NS (“saline responsive’)

• metabolic alkalosis and U[Cl] >10 = losing HCl via kidneys
• -> diuretics (loop, thiazide) or channelopathyies (Bartter, Gitelman)
• Cl and K wasting –> alkalosis as HCO3 retained for electroneutrality
• volume depletion –> alkalosis by RAAS

Question 18

Causes of hypoK: excretion - renal, hypertension

Answer 18

U[K] >20 + HYPERTENSION
- metabolic alkalosis and U[Cl] >10
==> Mineralocorticoid excess!

Hyperaldosteronism

• Low renin, high aldo = primary (Conn’s); ddx adenoma, hyperplasia
• high renin, high aldo = secondary e.g. RAS, Renin-secreting tumour

Cushing’s syndrome

• low/normal renin and aldo
• excessive cortisol activates mineralocorticoid receptor

Hyperaldosteronism mimics
- low renin, low aldo
DDx: Liddle syndrome (+ve ENaC), apparent mineralocorticoid excess (11-beta- HSD2 deficiency), licorice (inhib 11-beta-HSD2)

Question 19

Causes of hypoK: excretion - renal, others

Answer 19

U[K] >20

Metabolic acidosis

• RTA type I and II
• Carbonic anhydrase inhibitors

Normal acid-base (rare)

• HypoMg – increases renal excretion of K and decreases secretion and action of PTH
• cisplatin (cause hypoMg)

Question 20

Pearl

Answer 20

HypoK with metabolic alkalosis should always consider aldosterone excess!

U[K] and U[Cl] rarely checked in reality as clinical causes are usually obvious

Question 21

Treatment of HypoK

Answer 21

Treat underlying cause
Correct dehydration (saline response)

Replace K

• • oral syrup KCl is safest
• • IV KCl if K<2.5mM (must give slowly at low concentration)
• • never bolus KCl!!

Question 22

Diuretics causing dyskalemia

Answer 22

HyperK = K sparing diuretics

• aldosterone antag
• ENaC blockers

HypoK = thiazide, loop

• thiazide: hyperCa
• loop: hypoCa