Normal Plasma K+ concentration 3.

5 5mmol/L Major intracellular cation

K+ in the ECF <2% of the total body content ICF/ECF=38:1

K+ intake-40-120 mmol/day,90% of which is absorbed by the GI tract. Maintenance of steady state Extrarenal adaptive mechanism Urinary excretion

Major source of excretion-renal

Filtered load of K+ is 20 fold greater than ECF K+ content. 90% of filtered K+ is absorbed by the PCT & loop of Henle

Proximally K+is reabsorbed passively with Na & water. Luminal Na+-K+-2Cl- co transportermediates K+uptake in thick ascending limb of loop of Henle. Regulation of renal excretion & total K balance is regulated in the distal nephron

K+secretion Two physiological stimuli Aldosterone & hyperkalemia. K+ conc alone directly affects the K+secretion. Increased distal flow rate increases renal K+loss

Serum K+ concentration is determined by K+intake distribution between the cells & extracellular fluid urinary excretion of K+

Measurement Urine K+ levels A value above 80 to 100 meq/day increased potassium intake

Identifies condition that predisposes to hyperkalemia. Asymptomatic Generalised fatigue Paralysis Palpitations

Cardiac examination may reveal extrasystoles, pauses. Neurologic examination may reveal diminished deep tendon reflexes or decreased motor strength. In rare cases, muscular paralysis and hypoventilation may be observed. Search for the stigmata of renal failure, such as edema, skin changes, and dialysis sites. Look for signs of trauma that could put the patient at risk for rhabdomyolysis

Complete Blood Count Electrolytes BUN S.Creatinine S.Osmolality Urine osmolality

Mild Hyperkalemia(5.5-6.5mmol/L)-Tall peaked T waves with narrow base Moderate hyperkalemia(6.5-8 mmol/L)Peaked T waves Prolonged PR interval Decreased amplitude of P waves Widening of QRS complex

Severe HyperkalemiaAbsence of P waves Intraventricular blocks,BBB, Progressive widening of QRS complex Sine wave pattern ventricular fibrillation,asystole

Increased potassium release from cells

Reduced urinary potassium excretion

Pseudohyperkalemia Metabolic acidosis Insulin deficiency, hyperglycemia, and hyperosmolality Increased tissue catabolism -adrenergic blockade Exercise Other Digitalis overdose Hyperkalemic periodic paralysis Succinylcholine Arginine hydrochloride Hypoaldosteronism Renal failure Effective circulating volume depletion Hyperkalemic type 4 renal tubular acidosis Selective impairment of potassium excretion Ureterojejunostomy

Renal Failure Decreased distal flow(decreased effective arterial volume) Decreased K+secretion a)Impaired Na+ reabsorption 1)Primary hypoaldosteronism:adrenal insufficiency,adrenal enzyme deficiency

2)Secondary Hypoaldosteronism:Hyporeninemia,drugs (ACEI,NSAIDS,Heparin) 3)Resistance to aldosterone: Pseudohypoaldosteronism,tubulointerstitial disease,drugs(K+sparing diuretics,trimethoprim,pentamidine. b)Enhanced Cl-reabsorption 1)Gordons syndrome 2)Cyclosporine

The severity of Hyperkalemia is determined by Symptoms Plasma K+ concentration Electrocardiographic abnormalities

POTASSIUM ADAPTATION

due to more rapid potassium excretion in the urine

Increase K+ release from cells

Elevation in Serum K+ concentration due to movement of K+ out of the cells. Occurs In mechanical trauma during venipuncture Cooling of sample & specimen deterioration In leucocytosis>100000, thrombocytosis>400000

Metabolic acidosis Insulin deficiency,hyperglycaemia,hyperosmolarity Beta-adrenergic blockade Exercise Hyperkalemic Periodic Paralysis

In metabolic acidosis, more than one-half of the excess hydrogen ions is buffered in the cells. Electroneutrality is maintained in part by the movement of intracellular K+ into the extracellular fluid. Metabolic acidosis results in a plasma K+ concentration that is elevated in relation to total body stores. On average, the plasma K+ concentration will rise by 0.6 meq/L (range 0.2 to 1.7 meq/L) for every 0.1 unit reduction in extracellular pH.

Insulin promotes K+ entry into cells The ingestion of glucose (which stimulates endogenous insulin secretion) minimizes the rise in the serum K+concentration. Mechanisms of K+ out of cells. The loss of water raises the cell K+ concentration, thereby creating a favorable gradient for passive K+ exit.

Hyperosmolality-induced hyperkalemia Administration of hypertonic mannitol / development of hypernatremia. Somatostatin-postprandial hypotension cases fall in insulin levels Fasting in dialysis patients lowers insulin levels enough to cause clinically important hyperkalemia and resistance to betaadrenergic stimulation of K+uptake .

Trauma (including noncrush trauma) Administration of cytotoxic / radiation therapy to patients with lymphoma / leukemia (the tumor lysis syndrome)

Mechanisms mediated: A delay between K+ exit during depolarization and subsequent reuptake by the Na-K-ATPase pump. With severe exercise, there is increased number of open K+ channels in the cell membrane. These channels are inhibited by ATP, an effect that is removed by the exercise-induced decline in ATP levels which removes the inhibitory effect of ATP on these channels . The release of K+ during exercise may have a physiologically important role. The local increase in K+ concentration has a vasodilator effect, thereby increasing blood flow and energy delivery to the exercising muscle

Hyperkalemic form of periodic paralysis is an autosomal dominant disorder Episodes of weakness / paralysis are usually precipitated by cold exposure,/rest after exercise, fasting/ the ingestion of small amounts of potassium. The primary abnormality in hyperkalemic periodic paralysis - a point mutation in the gene for the alpha subunit of the skeletal muscle cell sodium channel.

The degree of potassium secretion is primarily stimulated by three factors: An increase in the serum potassium concentration A rise in the plasma aldosterone concentration Enhanced delivery of sodium and water to the distal secretory site

Chronic Hyperkalemia

Impaired secretion Diminished distal solute delivery

Decreased K+ Secretion

Primary hypoaldosteronism Congenital adrenal hyperplasia

HyporeninemiaDecrement in the angiotensin II production intradrenal defect-decline in aldosterone secretion Causes Diabetic Nephropathy-renal failure Chronic Interstitial Nephritis Features: Low plasma renin activity is common in diabetic patients dueto a defect in the conversion of the precursor prorenin to active renin the increase in atrial natriuretic peptide release in these patients can suppress both the release of renin and hyperkalemia-induced secretion of aldosterone

NSAID(Low PRA & aldosterone) Reduce renal secretion & vasodilatory renal prostaglandins Impair angiotensin II induced aldosterone secretion. ACEI,ARB Angiotensin I----Angiotensin II Angiotensin II Receptor Inhibits renin activity

Antibiotics Trimethoprim & pentamidine--- distal nephron Na reabsorption Heparin has a direct toxic effect on the adrenal zona glomerulosa cells Mediated by reduction in the number and affinity of adrenal angiotensin II receptors . Amiloride & triamterene block the apical Na channels in the principal cell

Pseudohypoaldosteronism Characterised by

Decreased excretion Increased distal flow rate & K+secretion compensate for the decreased renal mass. As GFR falls below10-15ml/min/oliguria ensues-hyperkalemia Other nephropathies Interstitial nephritis Lupus nephritis Sickle cell disease Diabetic nephropathy

Characterized by Hyperkalemia Metabolic acidosis Normal GFR Volume expanded with suppressed reninaldosterone levels as well as refractory to the kaliuretic effect of exogenous mineralocorticoids Due to incresed distal Cl-reabsorption

In cases where urinary potassium excretion is impaired TTKG= [Urine K (Urine osmolality / Plasma osmolality)] Plasma K TTKG in normal subjects is 8 to 9 Rises to above 11 with a K+ load, indicating increased K+ secretion

value below 7 and particularly below 5 in a hyperkalemic patient may be due to: Hypoaldosteronism resistence to renal effects of mineralocortricoid

Exclude pseudohyperkalemia Exclude transcellular shift Exclude oliguric renal failure Stop NSAID & ACEI
Assess K secretion TTKG<5
Response to 9a fludrocortisones TTKG>10 TTKG<10

TTKG >10

Decreased effective circulating volume Low protein diet

Primary/secondary hypoaldosteronism

Hypotension High renin/aldosterone

Pseudohypoaldosteronism

Hypertension Low renin/ aldosterone

Gordons syndrome Cyclosporine Distal type 4 RTA

Measure renin/aldosterone levels

K sparing diuretics Trimethoprim,pentamide

Hyperkalemia Movement of potassium out of the cells Administration of potassium to patients who are unable to excrete potassium in the urine due to 1)Advanced renal failure 2)Volume depletion 3)Hypoaldosteronism of any cause

Diagnosis of hypoaldosteronism

Drug / presence of a disease that can impair aldosterone release: Nonsteroidal antiinflammatory drug, Angiotensin converting enzyme (ACE) inhibitor Cyclosporine Heparin Acquired immune deficiency syndrome

It is associated with low PRA (in most but not all cases) low serum aldosterone concentration normal serum cortisol concentration.

low serum aldosterone Low cortisol concentrations, High PRA due to volume depletion and hypotension.

Hypoaldosteronism can result from a deficiency of enzymes required for aldosterone synthesis, which may or may not be associated with concurrent abnormalities in cortisol and androgen production, Low serum aldosterone Low cortisol concentrations, High PRA due to volume depletion and hypotension

Congenital isolated hypoaldosteronism is a rare inherited disorder-autosomal Recessive trait,defect in the aldosterone synthase (CYP11B2) Clinical Presentation recurrent dehydration salt wasting failure to thrive

These disorders can be differentiated by measurement of plasma renin activity (PRA) and serum aldosterone and cortisol These tests should be performed after the administration of a loop diuretic or three hours in the upright position, which will increase renin and aldosterone release in normals.

Determined plasma K+ concentration Muscular weakness ECG changes Fatal hyperkalemia-7.5mmol/L

Severe Hyperkalemia Minimizing membrane potential Shifting K+into the cells Promoting K+ loss

Treatment of Hyperkalemia

Cause Presence of symptoms & signs The most serious manifestations of hyperkalemia muscle weakness or paralysis, cardiac conduction abnormalities cardiac arrhythmias sinus bradycardia, sinus arrest, slow idioventricular rhythms, ventricular tachycardia, ventricular fibrillation, and asystole.

Occurs at serum pK concentration>7 Meq/L in chronic hyperkalemia Clinically manifests-in one or more ECG abnormalities with hyperkalemia

Continuous cardiac monitoring and serial electrocardiograms are warranted in patients with hyperkalemia on rapidly acting therapies. The serum potassium should be measured at one to two hours after the initiation of therapy.

Calcium directly antagonizes the membrane actions of hyperkalemia. Hyperkalemia-induced depolarization of the resting membrane potential leads to inactivation of sodium channels and decreased membrane excitability. The effect of intravenous calcium administration begins within minutes, but is relatively short-lived (30 to 60 minutes) The usual dose of calcium gluconate is 1000 mg (10 mL of a 10 percent solution) infused over two to three minutes, with constant cardiac monitoring.

The dose of either formulation can be repeated after five minutes if the ECG changes persist or recur.

Calcium Gluconate can be given peripherally, ideally through a small needle or catheter in a large vein. Calcium should not be given in bicarbonate-containing solutions, which can lead to the precipitation of calcium carbonate

When hyperkalemia occurs in patients treated with digitalis, calcium should be administered for the same indications as in patients not treated with digitalis (eg, widening of the QRS complex or loss of P waves) Hypercalcemia potentiates the cardiotoxic effects of digitalis A dilute solution can be administered slowly, infusing 10 mL of 10 percent calcium gluconate in 100 mL of 5 percent dextrose in water over 20 to 30 minutes, to avoid acute hypercalcemia

Insulin administration lowers the serum potassium concentration Drives potassium into the cells, primarily by enhancing the activity of the Na-K-ATPase pump in skeletal muscle Insulin should be given alone if the serum glucose is 250 mg/dL (13.9 mmol/L) The serum glucose should be measured one hour after the administration of insulin.

One commonly used regimen for administering insulin and glucose is 10 units of regular insulin in 500 mL of 10 percent dextrose, given over 60 minutes. Another regimen consists of a bolus injection of 10 units of regular insulin, followed immediately by 50 mL of 50 percent dextrose (25 g of glucose).

Hypertonic glucose in the absence of insulin may acutely increase the serum potassium concentration by raising the plasma osmolality, which promotes water and potassium movement out of the cells

The effect of insulin begins in 10 to 20 minutes, peaks at 30 to 60 minutes, and lasts for four to six hours. In almost all patients, the serum potassium concentration drops by 0.5 to 1.2 meq/L

Patients with renal failure are resistant to the glucose lowering effect of insulin, they are not resistant to the hypokalemic effect because Na-K-ATPase activity is still enhanced

Impaired renal function hypovolemia, nonsteroidal antiinflammatory drugs, urinary tract obstruction inhibitors of the renin-angiotensinaldosterone system

Diuretics Cation exchange resin Dialysis

Loop and thiazide diuretics increase potassium loss in the urine in patients with normal renal function.

The major available cation exchange resin is sodium polystyrene sulfonate. If a cation exchange resin is given, we prefer the preparation of sodium polystyrene sulfonate without sorbitol. In the gut, sodium polystyrene sulfonate takes up potassium (and calcium and magnesium to lesser degrees) and releases sodium. Each gram of resin may bind as much as 1 meq of potassium and release 1 to 2 meq of sodium. A potential side effect is exacerbation of edema due to sodium retention.

Dosing The oral dose is usually 15 to 30 g, which can be repeated every four to six hours as necessary. Single doses are probably ineffective. Lower doses of sodium polystyrene sulfonate (5 or 10 g) are generally well tolerated (no nausea or constipation), and can be given one to three times per day to control chronic asymptomatic mild to moderate hyperkalemia in patients with chronic kidney disease, often without the necessity of concurrent laxative therapy

50 g of sodium polystyrene sulfonate is mixed with 150 mL of tap water (not sorbitol). After a cleansing enema with tap water at body temperature, the resin emulsion should be administered at body temperature through a rubber tube placed at about 20 cm from the rectum with the tip well into the sigmoid colon . The emulsion should be introduced by gravity and flushed with an additional 50 to 100 mL of non-sodium-containing fluid.

The emulsion should be kept in the colon for at least 30 to 60 minutes and preferably two to four hours. A cleansing enema (250 to 1000 mL of with tap water at body temperature should follow.

Prevention

In Chronic Kidney disease ,in stable maintenance haemodialysis patients.

Low Potassium diet Avoid episodes of fasting. Avoid, if possible, drugs that raise the serum potassium concentration

Patients with chronic kidney disease or heart failure are often treated with RAAS inhibitors. Close monitoring of serum K+ concentration and estimated GFR The dose of RAAS inhibitors should be reduced with moderate hyperkalemia (serum potassium 5.5 meq/L) and discontinued if the serum potassium rises above 5.5 meq/L.

THANKYOU