Seminar on

ELECTROLYTE IMBALANCE

: POTASSIUM

Dr. Sachin Verma MD, FICM, FCCS, ICFC

Fellowship in Intensive Care Medicine

Infection Control Fellows Course

Consultant Internal Medicine and Critical Care

Web:- http://www.medicinedoctorinchandigarh.com

Mob:- +91-7508677495References : 1. Harrison’s Principles of Internal Medicine 16th edn.2. The ICU Book – Paul L Marino.3. Practical Guide line on fluid therapy – Dr. S. Pandya

POTASSIUM BALANCE Potassium is the major intracellular cation. The normal

plasma potassium concentration is 3.5-5.0 mmol/L,

whereas that inside the cells is about 150 mmol/L. The

extra cellular : intracellular ratio being 38 : 1.

Therefore the amount of K+ in ECF (30-70 mmol)

constitutes less than 2% of total body K+ content (2500-

4500 mmol).

FACTORS AFFECTING DISTRIBUTION OF K+ IN AND OUT OF CELL

Hormones

- Insulin

- Catecholamines

- β2 adrenergic agonist

- α adrenergic agonist Acid base balance

- Metabolic acidosis

- Metabolic alkalosis Cell turnover. Osmolality - in hyperosmolal states K+ diffuses out

of cell along with water due to solvent drag.

TOTAL DIETARY POTASSIUM INTAKE

Total dietary intake of K+ is 40-120 mmol/day or 1

mmol/kg/day.

90% of it is absorbed in GI tract

Sudden rise in plasma K+ is prevented by :

a) Shift of K+ into the cell by insulin.

b) Excess K+ excreted in urine.

POTASSIUM EXCRETION Renal excretion is the major route for elimination of dietary and

other sources of K+ excess.

The filtered load of potassium (GFR x plasma potassium concentration) = (180 L/d x 4 mmol/L = 720 mmol/day) is 10 to 20 fold greater than ECF potassium content.

90% of filtered potassium is absorbed in proximal convoluted tubule. It is absorbed passively with sodium and water.

Na+ K+ 2 Cl- cotransporter mediates K+ uptake in thick ascending limb of loop of Henle.

Contd….

POTASSIUM EXCRETION The cell responsible for K+ secretion in late distal convoluted tubule

and cortical collecting duct is the principal cell, the driving force being favourable electro chemical gradient across the luminal membrane of the principal cell.

The electrical gradient is created by electrogenic Na+ absorption leading to lumen negative trans epithelial potential difference (TEPD).

The adults uptake of Na+ by principal cell occurs via apical Na+ channel and is driven by low intracellular Na+ concentration relative to lumen of CCD.

The mechanism of transport of Cl- in distal nephron is less clear.

Contd….

Contd….

POTASSIUM EXCRETION The cell responsible for K+ secretion in late distal convoluted tubule

and cortical collecting duct is the principal cell, the driving force being favourable electro chemical gradient across the luminal membrane of the principal cell.

The electrical gradient is created by electrogenic Na+ absorption leading to lumen negative trans epithelial potential difference (TEPD).

The adults uptake of Na+ by principal cell occurs via apical Na+ channel and is driven by low intracellular Na+ concentration relative to lumen of CCD.

The mechanism of transport of Cl- in distal nephron is less clear.

Contd….

HYPOKALEMIA It is potassium concentration less than 3.5 mmol/L.

CAUSES :

1. Deceased intake

a) Starvation

b) Clay ingestion (geophagia) – it binds dietary K+ and iron.

2. Redistribution into cell

A) Metabolic alkalosis – due to K+ redistribution into the cell as well as increased K+ loss (renal).

B) Hormonal

1. Insulin

2. β2 adrenergic agonist – it causes K+ influx into the cell as well as stimulates insulin release.

3. α adrenergic antagonist.

Contd..

CAUSESC) Anabolic States

1. Vitamin β12 or folic acid (red blood cell production).

2. Granulocyte macrophage colony stimulating factor.

3. Total parenteral nutriton

D. Others

1. Pseudohypokalemia

2. Barium toxicity

3. Hypothermia

4. Hypokalemic periodic paralysis.Contd….

CAUSES3. Increased loss

A. Nonrenal 1. Gastrointestinal

a) Diarrhoea b) Vomiting2. Integumentary

B. Renal : Increased distal flowa) Diuretic b) Osmotic diuretic c) Salt westing nephropathy.

C. Increased renal secretion of K+ a) Mineralocorticoid excess1. Primary hyper aldosteronism

- Adenoma (Conn’s syndrome)- Hyperplasia.- Carcinoma.

Contd….

CAUSES2. Secondary hyperaldosteronism

3. Apparent mineralo corticoid excess.

4. Congenital adrenal hyperplasia.

5. Cushing syndrome

6. Bartter’s syndrome.

b. Distal delivery of non-reabsorbed anion :

- Vomiting, nasogastric suction, type 2 (proximal) RTA, Toluene abuse, penicillin derivatives.

Others

- Amphotericin B - Liddle’s syndrome - Hypomagnesemia

Malignant hypertension

Renal artery stenosis

Renin secreting tumors

Hypovolemia

liquorice Chewing tobacco Carbenoxolone Na+

LIDDLE’S SYNDROME Autosomal dominant mode of inheritance. Hypertension Hypokalemia Metabolic alkalosis Renal K+ wasting. Suppressed renin and aldosterone secretion.

BARTTER’S SYNDROME ECF volume contraction Juxtaglomerular hyperplasia. Hyperreninemic hyperaldosteronism. Hypokalemia Metabolic alkalosis.

EFFECT OF HYPOKALEMIA AND THEIR CLINICAL FEATURES

The clinical manifestations of potassium depletion vary greatly between individual patients and their severity depends on the degree of hypokalemia. Symptoms seldom occur unless the plasma potassium concentration is <3 mmol/L.1. Neuro muscular

a. Skeletal muscle weakness :- fatigue- Myalgia- Muscular weakness in lower extremities –

Complete paralysis.b. Smooth muscles – paralytic ileus.c. Respiratory muscle weakness – hypoventilation.d. Tetanye. Rhabdomyolysis

Contd..

EFFECT OF HYPOKALEMIA AND THEIR CLINICAL FEATURES

2. Renal- Poly urea (Nephrogenic) diabetic insipidus.- Increased ammonia production.- Increased bicarbonate reabsorption.

3. Hormonal- Decreased insulin secretion.- Decreased aldosterone secretion.- Insulin resistance.

4. Metabolic- Negative nitrogen balance- Encephalopathy in patients with liver diseae.

5. Cardio Vascular- ECG changes/dysrrhythmia- Myocardial dysfunction

ELECTROCARDIOGRAPHIC FEATURES OF HYPOKALEMIA

The electro cardiographic chanes of hypokalemia are due to delayed ventricular, repolarisation and do not correlate well with plasma potassium concentration.

Early changes include

1. Flattening or inversion of the T wave

2. Prominent U wave

3. ST segment depression

4. Proloned Q.U. interval Severe potassium depletion may result in

1. Prolonged PR interval

2. Decreased voltage and widening of the QRS complex

3. An increased risk of centricular, arrhythmias especially in patients with myocardial ischemia or left ventricular hypertrophy.

HYPOKALEMIA

- Careful hisotry e.g. diuretic & laxative abuse, vomiting.

- exclude pseudo hypokalemia e.g. with marked leuko cytosis (AML) and normokalemia patients with low plasma K+ (It is due to WBC uptake of K+ at room temperature.

- eliminate decrease intake (e.g. starvation, geophagia) and intracellular cause (e.g. metabolic alkalosis, insulin therapy, beta 2 agonist administration stress, hypokalemic periodic paralysis, ananbolic states, massive transfusion

- Asssess urinary excretion (to clarify source of K+ loss)

* The appropirate response at K+ depletion is to excrete less than 15 mmol/day of K+ in the urine – due to increased reabsorption and decrease distal secretion.

CLINICAL APPROACH

TRANSTUBULAR POTASSIUM GRADIENT OR TTKG

This is ratio of K+ concentration in lumen of

cortical collecting duct (CCD) to that of potassium

concentration in plasma.

K+ [CCD] K+(u) ÷ osm (u) /osm (p) TTKG = ------------- = --------------------------------

K+ [P] K+ [P]

URIANRY K+ EXCRETION

>15 mmol/day<15 mmol/day

Assess K+ secretionAcid base status

TTKG>4Metabolic acidosis Metabolic alkalosis TTKG<2

Acid base status

Lower GIT K+ loss

• Mineralocorticoid excess• Liddle’s syndrome

• Na waisting nephropathy

• Osmotic diuresis• Diuresis

Metabolic alkalosisMetabolic acidosis

Hypertension• Diabetic ketoacidosis• Proximal type 2 RTA• Distal type-1 RTA• Amphotericin-B

Yes No

• Remoted diuretic use.• Remote vomiting.• K+ loss via sweating

• Vomiting • Bartter’s syndrome• Exclude diuretic abuse• Hypo magnesemia

TREATMENT The therapeutic goals are to correct the potassium deficit and to minimize

ongoing losses. It is generally safer to correct hypokalemia via oral route. A decrement of 1 mmol/L in the plasma potassium concentration (from 4.0 to 3.0

mmol/L) may represent a total body potassium deficit of 200 to 400 mmol. For every 1 mmol/L potassium depletion – A potassium deficiency is = 10% of

total body potassium stores (2500-4500 mmol). Patients with plasma levels under <3mmol often require in excess of 600 mmol of

potassium to correct the deficit. Patients with severe hypokalemia or those unable to take anything by mouth

require intra venous replacement therapy with Kcl (Potassium chloride). The maximum concentration of administered potassium should be no more than

40 mmol/L via a peripheral vein or 60 mmol/L via central vein. The rate of infusion should not exceed 20 mmol/hr unless paralysis or malignant

ventricular arrhythmia are present.

HYPERKALEMIA Defined as a plasma potassium >5.0 mmol/L occurs as a

result of either potassium release from cells or decreased renal loss.

Iatroenic hyperkalemia may result from over zealous parenteral potassium replacement or in a patients with renal insufficiency.

Pseudohyperkalemia

- Represents an artificially elevated plasma potassium concentration due to potassium movement out of

cells immediately prior to a following venipuncture, contributing factors include prologned use of a tourniquet with or without repeated fist cleneching, haemolysis and marked leukocytosis or thrombocytosis.

CAUSES OF HYPERKALEMIA Renal failure Decreased distal flow (i.e. decreased effective circulatory arterial

volume. Decrease K+ potassium secretion.

A) Impaired Na+ reabsorption1. Primary hypoaldosteronism

a) Adrenal insufficiencyb) Adrenal enzyme deficiency : 21-hydroxylase, 3 β

hydroxysteroid dehydrogenase, corticosterone methyl oxidase.

2. Secondary hypoaldosteronism HyporeninemiaDrus (ACE inhibitors, NSAIDs, Heparin)

3. Resistance to aldosterone Pseudohypoaldosteronism Drus (K+ sparing diuretics, trimethoprim, pentamidine)

B) Enhanced Cl- reabsorption1. Gordon’s syndrome2. Cyclosporine3. Type IV RTA

CAUSES OF HYPERKALEMIA

C) Shift of potassium out of cell

1. Tissue damage (ischemia or shock) severe

exercise.

2. Metabolic acidosis.

3. Uncontrolled diabetes due to insulin deficiency.

4. Aldosterone deficiency.

5. Hyperkalemic periodic paralysis, succinyl

choline.

D) Tissue breakdown

1. Bleeding into soft tissue, GI tract or body

cavities.

2. Haemolysis, rhabdomyolysis

3. Catabolic state

GORDON’S SYNDROME Rare condition. Characterised by hyperkalemia/metabolic acidosis. Normal GFR. Volume expansion. Suppressed renin and aldosterone levels.

HYPERKALEMIC PERIODIC PARALYSIS Rare autosomal dominant disorder. Characterised by episodic weakness or paralysis

precipitated by stimuli that lead to mild hyperkalemia e.g. exercise.

CLINICAL FEATURES Hyperkalemia is often asymptomatic until plasma K+

concnetration is >6.5 to 7.0 mEq/L and may lead to fatal cardiac arrhythmia hence it is called as silent Killer.

Vague muscular weakness is usually first symptom of hyperkalemia.

Severe hyperkalemia can lead to hyporeflexia, gradual paralysis effecting initially legs then trunk and arms and at last face and respiratory muscle.

Leg Trunk Arms Face Respiratory Paralysis usually spares the muscles supplied by cranial

nerves and patients remain alert and apprehensive until cardiac arrest and death occurs.

Contd….

CLINICAL FEATURES The most serious effect of hyperkalemia is cardiac

toxicity, which does not correlate well with plasma potasium concentration.

The earliest electrocardio graphic changes – include increased T. wave amplitude or peaked T wave.

Serum K+ ECG findings

6-7 mEq/L Tall peaked T waves

7-8 mEq/L Loss of P waves and progressive widening of QRS complex.

8-10 mEq/L QRS merges with T waves forming sine waves

> 9 mEq/L Antrioventricular dissociation, ventricular tachycardia or fibrilation or asystole.

DIANGOSIS With rare exception, chronic hyperkalemia is always due to

impaired potassium excretion. If the etiology is not readily apparent and the patients is asymptomatic – pseudohyperkalemia should be excluded.

Oliguric acute renal failure and severe chronic renal insufficiency should be ruled out.

History should focus on medications that impair potassium handling and potential sources of potassium intake Evaluation of the Ecf compartment, effective circulatory volume and urine output are essential components of the physical examination.

The severity of hyperkalemia is determined by the symptoms, plasma potassium concentration and ECG abnormaliteis.

The appropriate renal response to hyperkalemia is to excrete at least 200 mmol of potassium daily. In most cases diminished renal potassium loss is due to impaired potassium secretion, which can be assessed by measuring the trans tubular potassium concentration gradient (TTKG).

APPROACH TO HYPERKALEMIA Exclude pseudohyperkalemia. Exclude transcellular K+ shift. Exclude oliguric renal failure. Stop NSAIDS and ACE inhibitors.

Assess K+ secretion

TTKG<5 TTKG>10 increased distal flow

• Decreased effective circulatory volume.• low protein diet [decreased urea] Response to 9-α Fludro-cortisone

TTKG>10 TTKG<10

• Pseudohypoaldosteronism• K+ sparing diuretics• Trimethoprim• Pentamidine

• Gordon’s syndrome• Cyclosporine• Distal type IV RTA

Primary or secondary hypoaldosteronism

Measure renin and aldosterone levels

• Hypotension• High renin and aldosterone

• Hypertension.• Low renin aldosterone

TREATMENT The need to treat hyperkalemia, how urgently and how aggressively, depends on its

degree clinical status.EMERGENCY TREATMENT. Potentially fatal hyperkalemia (serum potassium >7.5 mmol/L). Profound weakness, absence of P wave, QRS widening or ventricular arrhythmia on

ECG needs urgent treatment. It is based on following principle :

A) antagonism of membrane effects hyperkalemia – Inj. Calcium gluconate.B) Potasium movements into the cells – inj. Insulin and glucose.

- Inj. sodium bicarbonate.- beta 2 adernergic agonsit salbonate.

C) Removal of potassium from the body - Loop or thiazide diuretics- Cation exchange resin (Keyxalate)- Peritoneal dialysis or haemodialysis.

CALCIUM GLUCONATE Calcium gluconate injection is available as 10% solution in 10 ml ampules. The usual dose is 10-20 ml infused over 5 to 10 minutes. It is the most rapid treatment available and effect begins within minutes but is

short lived 30-60 minutes. The dose can be repeated if no changes in ECG is seen after 5-10 minutes.

Calcium administered decreases membrane excitability and protects the myocardium from toxicity due to potassium.

It should be remembered that calcium does not lower serum potassium level, so definite treatment should be planned.

Calcium can exacerbate or precipitate digitalis induced arrhythmia. As a result calcium should be avoided if patient is on digitalis therapy or if necessary should be used with great care.

Contd….

INSULIN & GLUCOSE Fast way to lower serum potassium. Insulin causes potassium to shift into cells. Glucose is

administered with insulin to prevent hypoglycemia. Administer 25 to 50 gms of glucose together with 10-20

units of regular insulin. Dose of insulin is reduced to 50% in a patient with severe

renal impairment. Initial bolus of glucose insulin should be followed by

infusion of 5% dextrose at 100 ml/hr to prevent late hypolycemia.

If effective, the plasma potassium concentration will fall by 0.5 to 1.5 mmol/L. This effect begins in 15 minutes peaks at 60 minutes and may last for approximately 4-6 hours.

Contd….

SODIUM BICARBONATE INFUSION Alkali therapy with I/V NaHCO3 will shift potassium into the

cells. Sodium bicarbonate 7.5%, 50-100 ml (45-90 mEq) is given as bolus I/V slowly over 10-20 minutes followed by I/VNaHCO3 drip – (3 amp in 1 Lt. NS) and ideally should be reserved for severe hyperkalemia associated with metabolic acidosis.

Onset of its effect is 5-10 minutes and effect lasts for 1-2 hours. The injudicious use of large amount of alkali can cause excessive calcium binding to albumin and provokes tetany.

Care should be taken to avoid contact between calcium gluconate and soda bicarbonate in the needle, syringe or infusion set – as it will precipirate into chalky deposits.

The patients with CRF –ESRD seldomn respond to this therapy and may not tolerate the sodium load and the resultant volume expansion.

Contd….

BETA ADRENERGIC AGONISTS Beta 2 agonist such as salbutamol – promote cellular uptake

of potassium and effectively lower serum potassium level. Salbutamol is given in a nebulized form or parenterally dose

recommended is 20 mg in 4 ml of salin by nasal inhalation ove 10 minutes or 0.5 mg by I/V infusion.

It generally becomes effective in 30 to 60 minutes and its effect – persists for 2 to 4 hours. It lowers serum potassium level by 0.5 to 1.5 mEq/L.

Insulin and beta agonist exert additive effect. I/V salbutamol is preferred in ESRD required a rapid lowering of serum potassium. However, nebulisation is preferred in ESRD patient associated with CAD because heart rate is less elevated with nebulisation than I/V therapy.

Contd….

LOOP & THIAZIDE DIURETICS Often in combination therapy may enhance potassium

excretion,if renal function is adequate.

CATION EXCHANGE RESINS Cation exchange resins such as sodium polystyrene sulphonate

(Key xalate) promote the exchange of sodium for potassium in GI tract. Each gram binds 1 mEQ of potassium and release 2-3 mEq of sodium.

When given orally the usual dose is 25-30 gram mixed with 100ml of 20% sorbitol resins and 50 ml of 70% sorbitol mixed in 150 ml water every 4-6 hours as retention enema. It is retained for about 60 minutes after which rectum is washed with clear water. The rectal route is faster and more reliable.

Each enema can generally lower the plasma potassium concentration by 0.5 to 1.0 mEq/L within 1-2 hours and effect will last for 4-6 hours.

Contd….

DIALYSIS

The most rapid and effective way of lowering the plasma potassium concentration is haemodialysis (removal rate 35 mEq/hour).

Dialysis should be reserved for patient with renal failure and those with severe life threatening hyperkalemia unresponsive to more conservative measures.

Peritoneal dialysis also removes potassium but is only 15-20% as effective as haemodialysis.

NON EMERGENCY TREATMENT (Mild to moderate hyperkalemia)

1. DIETARY POTASSIUM RESTRICTION

- Avoid fruit juice, coconut water and food rich in potassium.

2. AVOID MEDICATION

- Potassium sparing diuretics, NSAIDS and ACE inhibitors (all decreased potassium excretion).

- Beta blockers (decrease ECF to ICF shift of potassium).

3. LOOP OR THIAZIDE DIURETICS

- increased renal excretion of potassium.

4. Cation exchange resins

- dose required 15-20 gm keyxalate, 2-4 times/day.

5. Specific etiological treatmetn

- Addison’s disease – glucocorticoid (hydro cortison) therapy.

- Hypoaldosteronism : mineralocorticoid supplement 0.2 mg/day (Fludrocortisone).

- Hyperkalemia periodic paralysis – prophylactics beta 2 agonsit inhalation.

- Treatment of diabetic ketoacidosis.

- Correct volume depletion.

- Correct metabolic acidosis. Metabolic acidosis is generally associated with hyperkalemia so treat

with soda Bicarb (600 tab. 2-3 times per day) or sodium citrate (Shohl’s solution 10-15 ml TDS).