Hypokalemia Dr. Anil kumar.H Assistant professor Department of pediatrics , BMCRI CME on fluid and electrolytes , BMCRI , 13/08/2017

K Homeostasis Clinical implications Etiology Approach and evaluation Management

Nak ATPase

Adults maintain zero potassium balance Infants and children have positive potassium balance .

K Homeostasis Internal homeostasis External homeostasis

Factors altering K distribution ↑ Uptake ↓ uptake ( shift out ) Insulin β2 agonists Alkalosis Acidosis Sternous excercise Hyperosmolality

Insulin & β2 agonists

Acidosis

Alkalosis

External homeostasis

External homeostasis

cv BS 1 cvv BS 4 BS 2 cvv b BS 3

The amount of K reabsorbed in the PCT and LOH is a constant fraction of the amount filtered.

External homeostasis

cv GITELMAN SYNDROME

External homeostasis

Determinants of K secretion Aldosterone Distal delivery of Na and water

Aldosterone Stimulates Na⁺-K⁺-ATPase activity Increases Na reabsorption Increases luminal membrane permeability to K

Hence , late DCT and CCD plays an important role in K regulation.

Clinical implications

Functions of K IC : EC ratio is required for maintaining RMP of cells . High intracellular K concn. is essential for many cellular processes: DNA and protein synthesis Cell growth and apoptosis Mitochondrial enzyme function Conservation of cell volume and pH.

Cardiovascular effects Cardiac arrythmias Premature atrial and ventricular beats Sinus bradycardia AV blocks VT or VF Increased SVR ( HTN)

Neuromuscular disturbances ( Hyperpolarization of muscles and ↓ blood flow to muscles ) Skeletal muscle weakness Muscle cramps, Rhabdomyolysis Smooth muscle dysfunction ( GI and urinary system )

Renal effects ↓ urinary concentrating ability ( ↓ AQP2 expression ) ↑ Renal ammonium production → ↑ HCO3 ( Metabolic alkalosis) Hypokalemic nephropathy ( IF, TA, cyst formation in renal medulla)

External homeostasis

Endocrine and metabolic effects Growth retardation Glucose intolerance ( ↓Insulin release and end organ sensitivity) ↓ Aldosterone release Hepatic encephalopathy ( susceptible individuals )

Etiology

Spurious hypokalemia

Spurious hypokalemia Metabolically active cells take up K from plasma No clinical manifestations and ECG is normal Prevented by immediately separating plasma and storing at 4ºC.

2. Transcellular shifts Insulin Endogenous : Refeeding syndrome Exogenous : Treatment of DKA Metabolic alkalosis β2 agonists Endogenous: stress, hypothermia Exogenous : Salbutamol Hypokalemic periodic paralysis ( recurrent , pptd)

Insulin & β2 agonists

Alkalosis

Total body potassium depleted Decreased intake Extrarenal loss ( GI, Sweat) Renal loss

Decreased intake PEM Anorexia Nervosa

Extrarenal loss 2 yr old child comes with loose stools for 2 days, o/e- severe dehydration S.E- 140/2.5/117 ABG- Metabolic acidosis 000

Average composition of diarrhea Sodium : 55 meq/l Potassium : 25 meq/l Bicarbonate : 15 meq/l Lower GI loss is associated with acidosis

Other causes of lower GI loss Laxative abuse K binders

17 yrs old child ( MAY 2017 ) Vomitting – on and off – 2yrs Abdominal pain , weakness – 6 mths Had 15 admissions in 2 yrs P/A: Intestinal loops seen

SE- 125/2.5/72 RFT – 127/1.6 ABG : USG Abdomen- S/o intestinal malrotation with midgut volvulus RK- 9.8 cms, LK- 8.5 cms Diffuse ↑ in cortical echogenecity with loss of CMD

Average composition of gastric fluid Sodium - 60 meq/l Potassium – 10 meq/l Chloride -90 meq/l Loss of H+ Upper GI loss- Metabolic alkalosis

Other non renal Cystic fibrosis Full thickness burns

Upper GI loss, ↑ sweat ↓ ECV depletion RAAS activation Hypokalemia

Urinary K will not differentiate renal from extrarenal loss

Renal loss

4 mths old baby Not gaining weight since birth Hurried breathing -2 days Refusal of feeds - 2 days Birth wt-3 kgs, present wt- 2.07 kgs Admission at 1 1/2 mths for fever

O/E – Dehydrated, Acidotic breathing + Labs - ABG : 7/20/356/5.8/-25.3 SE - 150/3.3/131 AG: 16 ( NAGMA) Urine pH – 7 USG KUB : B/l medullary nephrocalcinosis

Diagnosis ? Distal RTA Treated with shohls solution and potassium citrate

Hypokalemia in RTA In Fanconi syndrome, Volume depletion leads to RAAS activation. ↑ Na delivery to distal tubules

Renal loss with acidosis Renal tubular acidosis DKA Acetazolamide

1 ½ mths female baby ( Nov 2016) Abd.distension - 2 days Refusal feeds - 1 day Reduced activity - 1 day No h/o fever On EBF , No previous hosp. FTND, B.wt- 2.1 kgs

o/e - lethargic , dehydration + wt -2.5 kgs P/A ; Distended, liver 3cm BCM, no FF Diagnosis : ? Sepsis ??

Labs CBC: 10.6/ 12,200/ RFT- 32/0.31 ABG: 7.6/47/221/42.3/+23…. K- 1.3 ECG monitor- inverted T waves, ? U wave SE: 138/4.2/109

Urine Cl - 116 meq/L Urine K – High

DIAGNOSIS ? BARTTERS SYNDROME

Subsequent SE…. 30/11 1/12 3/12 4/12 Na 135 138 132 120 127 K 2.3 2 1.9 2.7 Cl 88 86

Subsequent ABGs 29/11 30//11 1/12 3/12 8/12 PH 7.6 7.59 7.67 7.56 7.65 HCO3 42.3 46.8 41.8 37 44 BE 23 24.5 21 16.3 26

Hypokalemia with metabolic alkalosis with low or normal BP Bartters syndrome Gitelmans syndrome Loop diuretics Thiazide diuretics

cv BS 1 cvv BS 4 BS 2 cvv b BS 3

cv GITELMAN SYNDROME

13 Yr old boy Presented with headache, photophobia, projectile vomiting and convulsions 4 days back No h/o fever /neck pain/altered sensorium No history s/o focal neurologic deficit No past history of seizures

He was evaluated in another hospital, found to be hypertensive – 210/110 mm Hg, treated with labetalol infusion and Inj. phenytoin

On examination PR-90/min, BP Rt UL- 150/100 mm Hg Lt UL- 146/100 mm Hg Rt LL – 150/96 mm Hg Lt LL - 146/92 mm Hg No pallor / edema CNS : HMF- normal Pupils b/l ERL No FND P/A : No renal bruit No organomegaly

Investigations CBC: Hb- 11.8g%, TC-12,150, DC-79/16, PLC-3.4 lac BU-25, S.Cr-0.8 SE : 131/3/94 Urine – albumin 2+, no RBCs, 8-10 WBCs ABG : 7.46/41/219/29.2

Hypokalemia with metabolic alkalosis with hypertension ??

Rt Renal artery stenosis

Hypokalemia with metabolic alkalosis with HTN Mineralocorticoid excess

With mineralocorticoid excess Apparent MC excess ( AME ) Gucocorticoid remediable aldosteronism (GRA) Liddle syndrome Renovascular HTN

LIDDLE SYNDROME AME

Renal loss ( No spcefic AB dist. ) Recovery from AKI Post obstructive diuresis Interstitial nephritis Drugs Aminoglycosides Amphotericin –B Cisplatin

Etiology ( summary ) Spurious hypokalemia Decreased intake Transcellular shifts Extrarenal loss GI with acidosis – lower GI loss with alkalosis - upper GI loss Skin loss

Renal loss With metabolic acidosis- RTA, DKA With metabolic alkalosis- Bartter , Gitelman syn., loop and thiazide diuretics No sp. AB abn.- AKI recovery, postobstructive diuresis. Interstitial nephritis With MC excess - RAS, AME, GRA , Liddle syndrome

Approach and evaluation of Hypokalemia

Clinical setting usually gives clue : GI loss Recovery phase of ATN DKA Diuretics

ECG… ECG…. Life saving Repeated BP measurement ABG High BP with metabolic alkalosis – Mineralocorticoid excess

Renal potassium handling Spot urine K > 20 meq/l – abnormal loss Spot K/Cr ratio - > 13meq/g FEK- > 6 % is inappropriate response These differentiate transcellular shifts from K loss, not renal from extrarenal losses.

Urine Cl- Hypokalemia and metabolic alkalosis Differentiates renal from extrarenal losses Urine Cl- >20 meq/L indicates renal loss

PRA and PAC HTN , Hypokalemia and MA

HYOPOKALEMIA(R/O spurious hypokalemia) Urine K K/Cr FEK Urine K < 20 K/Cr <13 FEK <6 Urine K > 20 K/Cr >13 FEK >6 TC shifts Diarrhea , burns Renal loss Blood pressure Normal High PRA PAC M.Alkalosis M.Acidosis Urine Cl RTA DKA Acetazolamide ↑PRA ↑PAC ↓PRA ↑PAC ↓PRA ↓PAC Low < 20 meq/L Vomitting CF High > 20 meq/L BS GS Diuretics RAS RST GRA Adrenal adenoma Liddle AME CAH

Management IV supplementation is indicated in: Symptomatic patients with severe hypokalemia (< 2.5meq/L) ECG abnormalities Respiratory muscle weakness

Aim is to increase serum K to > 3 meq/L in 1-2 mins ( 3-obs. K ) x BW x 0.04 Rate of infusion should be 0.3-0.5meq/kg/hr

In transcellular shifts 0.5-1meq/kg/dose of Kcl is given over 1-2 hrs Infusion rate should not exceed 1 meq/kg/hr Concn. Should not exceed 60meq/l ( peripheral) and 80meq/l in central line .

Should not be mixed with dextrose solution Hypokalemia should be corrected before correction of acidosis.

In c/c hypokalemia , as in BS, IC:EC ratio is maintained at the cost of TB K wasting Oral potassium can be given Potassium chloride is preferred.

In RTA , oral potassium can be started Correct potassium before correction of acidosis Potassium citrate is preferred .

Overcorrection can lead to hyperkalemia , particularly in transcellular shifts Should be given under ECG monitoring

Potassium preparations Parenteral KCl solution --- 1 ml = 2meq K Oral KCl ( potklor ) .. 15 ml = 20 meq Oral K citrate ( potrate ) 1 ml = 2 meq K Potassium phosphate ( DKA ) , not available freely .

Other drugs in specific situations Indomethacin – Bartters syndrome Amiloride - Liddles syndrome Spironolactone

Key messages Most of the times there is a clue to etiology Causes - Transcellular shifts, renal and Extrarenal losses ECG when u suspect hypokalemia Check BP and ABG in all cases of hypokalemia Urine K+ does not differentiate renal from extrarenal loss Urine Cl- helps in differentiating renal from extrarenal cause

Oral K supplementation is safer except in life threatening situations Potassium chloride – alkalosis Potassium citrate – acidosis