Potassium - Physiology Potassium BalanceDr.R.Vaishnavi

Homeostasis:

Intake:

Regulation:

Potassium is the dominant intracellular cation (150 mEq/L) hence the plasma concentration (4 mEq/L) does not always reflect the total body potassium content.

The higher intracellular potassium gradient

1. Is used to produce the resting membrane potential of cells and is necessary for the electrical responsiveness of nerve and muscle cells and for the contractility of cardiac, skeletal, and smooth muscle.

2. Affects cellular enzymes

3. Is necessary for maintaining cell volume because of its important contribution to intracellular osmolality.

The Na+,K+-ATPase maintains the high intracellular potassium concentration by pumping potassium inside cell against concentration gradient and counteracts the effects of concetration dependent potassium channels.

Insulin and β-Adrenergic agonists stimulate the Na+,K+-ATPase, increasing cellular uptake of potassium.

Acidosis cause hyperkalemia and alkalosis cause hypokalemia by altering potassium distribution via potassium channels and the Na+,K+-ATPase.

Plasma osmolality changes causes potassium shifts as potassium follows water due to

Potassium -1-2 mEq/kg is the recommended intake. 90% of ingested potassium is absorbed primarily in small intestine

Excretion : Through urine, stools and skin. 90% of daily ingested K+ is excreted through urine and about 10% is excreted through the colon. The total output remains approximately the same as the total intake. The kidneys principally regulate longterm potassium balance. Colon exchange body potassium for luminal sodium and helps in intestinal potassium excretion in the setting of renal failure, hyperaldosteronism and glucocorticoid excess.

Distal tubule and collecting duct(CD), the principal sites of potassium regulation

Potassium is freely filtered at the glomerulus, 90% is resorbed in the proximal tubule and thick ascending limb of loop of Henle. K+ delivery to the distal nephron remains small and is fairly constant but the rate of K+ secretion by the distal nephron varies and is regulated according to physiologic needs.

The plasma potassium concentration directly influences secretion in the distal nephron. As the potassium concentration increases, secretion increases

In the CD, K secretion is by the principal cells (via luminal K channels and basolateral Na-K ATPase) and K reabsorption is by the alpha intercalated cells via a luminal H-K ATPase.The cellular determinants of K+ secretion in the principal cell include the intracellular K+concentration, the luminal K+ concentration, the potential (voltage) difference across the luminal membrane, and the permeability of the luminal membrane for K+.

Conditions that increase cellular K+concentration, decrease luminal K+ concentration, or render the lumen more electronegative will increase the rate of K+ secretion. Conditions that increase the permeability of the luminal membrane for K+ will increase the rate of K+ secretion.

 In the early DCT, luminal Na+ uptake is mediated by the apically located thiazide-sensitive Na+-Cl− cotransporter. The transporter is energized by the basolateral Na+-K+-ATPase, which maintains intracellular Na+ concentration low, thus providing a favorable gradient for Na+ entry into the cell through secondary active transport. The cotransporter is abundantly expressed in the DCT1 but progressively declines along the DCT2.

ROMK is expressed throughout the DCT and into the cortical collecting duct. Expression of the epithelial Na+ channel (ENaC), which mediates amiloride-sensitive Na+ absorption, begins in the DCT2 and is robustly expressed throughout the downstream connecting tubule and cortical collecting duct. The DCT2 is the beginning of the aldosterone-sensitive distal nephron (ASDN) as identified by the presence of both the mineralocorticoid receptor and the enzyme 11β-hydroxysteroid dehydrogenase II. This enzyme maintains the mineralocorticoid receptor free to only bind aldosterone by metabolizing cortisol to cortisone, the latter of which has no affinity for the receptor. Electrogenic-mediated K+ transport begins in the DCT2 with the combined presence of ROMK, ENaC, and aldosterone sensitivity. Electroneutral K+-Cl− cotransport is present in the DCT and collecting duct. Conditions that cause a low luminal Cl− concentration increase K+ secretion through this mechanism, which occurs with delivery of poorly reabsorbable anions, such as sulfate, phosphate, or bicarbonate.

Reabsorption of HCO3 in the distal nephron is mediated by apical H+ secretion by the α-intercalated cell. Two transporters secrete H+, a vacuolar H+-ATPase and an H+-K+-ATPase. The H+-K+-ATPase uses the energy derived from ATP hydrolysis to secrete H+ into the lumen and reabsorb K+ in an electroneutral fashion. The activity of the H+-K+-ATPase increases in K+ depletion and, thus, provides a mechanism by which K+depletion enhances both collecting duct H+ secretion and K+ absorption.

Two principal determinants of K+ secretion are mineralocorticoid activity and distal delivery of Na+ and water.

Aldosterone, the major mineralocorticoid is the principal hormone regulating potassium secretion.

1. It increases intracellular K+concentration by stimulating the activity of the Na+-K+-ATPase in the basolateral membrane. Second, aldosterone

2. It stimulates Na+ reabsorption across the luminal membrane, which increases the electronegativity of the lumen, thereby increasing the electrical gradient favoring K+ secretion.

3. It has a direct effect on the luminal membrane to increase K+ permeability

A second principal determinant affecting K+ secretion is the rate of distal delivery of Na+ and water.

Increased distal delivery of Na+  stimulates distal Na+ absorption luminal potential more negative increase K+ secretion.

Increased flow rates also increase K+ secretion.

K+ secreted in the collecting duct rises the luminal K+ concentration decreases the diffusion gradient slows additional K+ secretion.

At higher luminal flow rates, the same amount of K+ secretion will be diluted by the larger volume such that the rise in luminal K+ concentration will be less.

Hence we can correlate how polyuria is associated with hypokalemia.

Alkalosis causes potassium to move into cells, including the cells lining the collecting duct. This movement increases potassium secretion, and because acidosis has the opposite effect, it decreases potassium secretion.

Potassium homeostasis-

Approach

Dyskalemia

•Any child kept NPO and on IVF at risk for dyskalemia •TTKG (transtubular potassium gradient) to used when in doubt (Normal 8-9)•TTKG={(urine [K+] ÷ (urine osmolality/plasma osmolality)} ÷ plasma [K+]} •Urine output(polyuria/oliguria) , Intake/output status , urine potassium(high/low), effective circulatory volume, urine sodium also are important to analyze.

HYPOKALEMIA K + <3.5 mEq/la) Exclude sampling error, redistribution (Transcellular shift)

b) Drugs: β agonists bronchodilators (salbutamol, terbutaline), epinephrine, nasal decongestants, ,Insulin infusion.

c) Periodic paralysis (familial), Refeeding

syndrome, d) Extracorporeal: post dialysis, post plasmapheresis

Determine drug exposure,dietory

deificit, GI or renal loss based on clinical status and history and examination ,if undetermined do Urine K +

<15 mEq/l >15mEq/l

Blood gas

Metabolic acidosisDecreased intake (PEM)GI losses with diarrheaSevere burns

Metabolic Alkalosis Excessive sweating (Cystic fibrosis)

Blood Pressure

High

Hyper Aldosteronism (1o )2o Hyperaldosteronism (CHF, Nephritic syndrome, cirrhosis)Liddle’s syndromeRenovascular hypertensionNon salt losing CAHD/D based on plasma renin & Aldosterone levels

Normal

Blood gas

Metabolic acidosisRTA,(type I and II) DKA,Acetazolamide

Metabolic alkalosis/ NormalVomiting, NG suction Amphotericin BDiuretic therapyBartter, Gitelman SyndromeMagnesium deficiency

CAH: congenital adrenal hyperplasia; RTA- renal tubular acidosis; DKA- diabetic ketoacidosis

Urine K +

K + <3.5 mEq/L

Poor dietary intake (PEM)Intracellular shifts MiscellaneousRenal loss

Metabolic alkalosis, β agonist agents, hypokalemic periodic

paralysis, insulin infusion

Drugs: diuretics (loop and thiazide) , osmotic diuretics Amphotericin B

Mineralocorticoid excess1o hyper Aldosteronism

, 2o

Hyperaldosteronism

(CHF, Nephritic syndrome, cirrhosis), Liddle’s syndrome , reno vascular hypertension

Metabolic alkalosis: Bartter syndrome, Gitelmansyndrome, Magnesium deficiency

Metabolic acidosis: RTA,(type I and II)

Vomiting, diarrhea, NG tube, laxatives, malabsortion, stoma

loss

GI loss

Sweat loss (cystic fibrosis)Dialysis (or

plasmapheresis)

Blood pressure

High Normal

Mild to moderate(usually asymptomatic)

K + 2.5 -3.4mEq/l

Severe (symptomatic)K + <2.5mEq/l

Mild weakness of limb muscles,paralytic ileus

More weakness of limbs and also trunk and respiratory muscles,

Gastric distension, cardiac arrhythmias: ST depression, low voltage T wave, U waves, PVC, complete heart block rarely, when < 2 sudden

rhabdomyolysis and paralysis possible

Diagnose and treat cause, replenish deficit, prevent life threatening arrythmia

Oral replacement preferred , IV only when oral not

tolerated/ contraindicatedOral potklor 20mEq/15 ml1-4 mEq/kg/day in 2 to 4

divided dosesMonitor levels

Treatment of hypokalemia

IV replacement maximum 0.5 to 1 mEq/kg for first hour, followed by 0.25mEq/kg/hr for 3 to 4

hours in NS(not glucose) with cardiac monitoring, monitor level post correction

Peripheral line upto 40mEq/LCentral/PICC line upto 80 mEq/L may go up

based on situation

HYPERKALEMIA K +

5.5mEq/l

Exclude spurious causes sampling error, torniquet use, squeezing, hemolysis, pseudohyperkalemia (hyperleuckocytosis, thrombocytosis) Plasma potassium might help !!

Estimate GFR (Renal function )

<15ml/min/1.73 m2 >15ml/min/1.73 m2

Decreased K +

excretion Acute kidney injury, ESRD, K + sparing diuretics, nephrotxic

drugs*LBW Preterm babies

Increased K + loadK + supplements (iv/oral/diet)Blood transfusionsTLS/hemolysisRhabdomyolysisBurns(hypercatabolism)

Plasma Aldosterone

Normal/HighK + sparing diuretics1o , 2o PHA, RTA type 4Post renal tranplant

Low

Plasma Renin

Low (hyporenin+hypoaldosterone)Diabetic NephropathyInterstitial NephritisObstructive uropathyDrugs

High/NormalCAH1o HypoaldosteronismAddison’s diseaseDrugs

*Drugs: spironolactone, amiloride, cotrimoxazole, ACE inhibitors, ARB, β

blockers,heparin, NSAIDS, cyclosporine, tacrolimus.CAH: congenital adrenal hyperplasia; PHA: pseudohypoaldosteronism; GFR: glomerular filtration rate; RTA: renal tubular acidosis; TLS: tumor lysis syndrome; ESRD: end stage renal disease;

Redistribution (transcellular shift)Metabolic aciidosis, hyperkalemic periodic

paralysis, insulopenia, β blockers

Poor Normal

K + >5.5 mEq/l

Common causes: squeezed sample, specimen delay, renal insufficiency, acidosis, post transfusion, Tumor lysis, new born age.

Muscle weakness, palpitation, nausea, paresthesia, arrhythmia with ECG changes

Yes

Treat as hyperkalemia

No

Drugs Yes

Stop drugs

Urine K + >30mEq/lTranscellular shift

Acidosis, rhabdomyolysis, hyperglycemia, burns

Urine K + <30mEq/lImpaired renal excretion

Renal insufficiency, adrenal insufficiency , hyporeninemic

hypoaldosteronism

No

ABG, GFR, urea , Creat, glucose, electrolytes, digoxin levels, CPK, Urine K +

β blockers, spironolactone, ACEI

Antagonize membrane effects, of K +

, push K + into cells, remove excess K + from body

Mild hyperkalemia

5.5 to 6.5mEq/l(usually asymptomatic)

Stop iv and oral K + supplements,

avoid K + rich diet, try to stop K +

retaining drugs

Severe hyperkalemia6.5 to 8 mEq/l and above

(symptomatic)

In the background of normal functioning kidney try NS bolus followed by proper hydration and loop diuretics (furosemide

1mg/kg) and infusion if fluid overload present

Muscle weakness, palpitation, nausea, paresthesia, arrhythmia with ECG changes

Calcium gluconate iv over 5 min under cardiac monitoring if arrythmia, insulin and glucose infusion over 20min, with salbutamol nebs over 20 min, sodabicarb in CKD or cardiac arrest, hemodialysis if refractory , PD takes minimum 6 to

8 hrs.

Rule out sample/lab error,hemolysis, hyperleukocytosis, thrombocytosis,

new born age

Treatment of hyperkalemia

Hyperkalemia management

•Rule out sampling and measurement error, look for symptoms and ECG findings if above 6.5 mEq/L. •ECG Changes : Progressive changes as per K + level,

tall peaked T waves, PR interval, QRS width, loss of P wave and sine wave, PEA.Sudden

rise of K + a/w ventricular tachycardia, AV block, ventricular fibrillation•Stop all sources of IV and oral potassium, reduce dietary potassium, avoid K + rich food, stop potassium retaining drugs like β blockers, spironolactone, ACEI, medical management based on the clinical status, renal replacement therapy (dialysis) if hyperkalemia refractory to medical management

ECG Changes with changes in serum potassium

How will you manage this child?

What are the symptoms and signs of hypokalemia?

How to correct potassium in this patient ? What is the role of oral potassium in this patient?

ER resident starts K+ correction in available peripheral line at 0.5mEq/kg/hr.

Patient develops severe pain at infusion site. What is the reason?

What is the maximum potassium concentration we can give in a peripheral line?

What are the complications of untreated hypokalemia in this patient?

What is the preferred K+ level in this patient?

Fig. ECG in hypokalemia

Case scenario 1. (Dr.K. Ekambaranath)

Case scenario 2. (Dr.K. Ekambaranath)

A 11mo old child with h/o loose stools for past 2 days.One episode from today morning semisolid in consistency,no vomiting now.O/e child alert active, mild hypotonia,no dehydration.Serum K 3.0 mEq/L,ABG normal.ECG normal.

A. How will you manage this child?

A 9mo old baby known case of CHD on antifailure medications, now admitted with c/o fever and loose stools for 2 days.

O/e child is lethargic, tachypneic, tachycardic. Bilateral basal creps +.

Inv –Na 138mEq/L,K 2.6mEq/L,ABG metabolic alkalosis

CASE SCENARIOS

Case Scenario 4. (Dr.Muthiah Periyakaruppan)

Case Scenario 5. (Dr.Krithika)

Case Scenario 6. (Dr. Krithika)

8 years old male child k/c/o VUR with reflux uropathy presenting to hospital with lethargy tiredness. Height < 2 SD for age, weight < 2 SD for age. BP 140/70mmHg. Urine output is normal. Investigations: Urea 50mg/dL, Creat 2.2mg/dL, K 6, Na 134, Cl 100, HCo3 14(mEq/L).. He is on oral calcium, oral Sodabicarb.

What is the diagnosis?

How do we manage his hyperkalemia?

How to prevent hyperkalemia in this patient?

4 day old 35 week neonate

Summer season – hot environment. Infant of diabetic mother

Poor feeding – excess wt loss. It was difficult sampling, crying baby, multiple pricks

Inadequate time between alcohol swabbing and pricking

Required squeezing . Collected in plain tube (red cap) and stored at room temperature

Analysed 3 hours after collection

Serum potassium 7.8 mEq/L

1. What is the next thing you do?2. What are the possible cause of pseudo-hyperkalemia you think in this child?

A 6yr old male child presented with acute watery diarrhoea, vitals-stable, systems normal, investigation revealed hypokalemia (k-2.5meq) acute potassium corrections given followed by double maintenance potassium in iv fluids. Diarrhoea settled, child active and stable. Planned for discharge, before discharge repeat potassium taken from peripheral line, it shows hyperkalemia (k-6.5meq).

1. What do you think is the cause and what is your next step?

Case Scenario 3. (Dr.Muthiah Periyakaruppan)

10 year old male child 30 Kg newly diagnosed with T-cell ALL with

TLC 100000, Plt-30000, Hb 6. electrolytes- Na+ 130mEq/L, K+ 7mEq/L, Cl 100mEq/L, Ca 6mg/dL, Phosphate 9mg/dL, Hco3 22mEq/L. He is planned for chemotherapy initiation.

What are the concerns in treating this patient?What are the other relevant investigations we want to know?He is also observed to have tall T waves after admission. What do we do?What are the other supportive measures for this patient?What if medical management fails to control electrolyte disturbance?What are the goals of treatment?

Hyperkalemia