Postgrad Med J 2001;77:759–764
Hypokalaemia and hyperkalaemia A Rastergar, M Soleimani compartments. Humans, as carnivorous ani- Disturbances in potassium homoeostasis
mals, consume large amount of potassium presenting as low or high serum potas-
intermittently. Dietary potassium, which is sium are common, especially among hos-
rapidly absorbed by the gut, could increase pitalised patients. Given the fact that
serum potassium dramatically. However, sev- untreated hypokalaemia or hyperkalae-
eral physiological mechanisms quickly shift the mia is associated with high morbidity and
potassium intracellularly, allowing slow excre- mortality, it is critical to recognise and
tion of potassium by the kidney, and mainte- treat these disorders promptly. In this
nance of normal potassium homoeostasis.1 article, normal potassium homoeostasis is
Normal physiological regulators, insulin and reviewed initially and then a pathophysi-
catecholamines, are stimulated by ingestion of ological approach to work-up and man-
food containing glucose and potassium. These agement of hypokalaemia and hyper-
hormones are essential in shift of potassium kalaemia is presented. Recent advances
intracellularly, depositing it primarily in the liver with respect to the role of kidney in
and striated muscle cells.2 Catecholamines, by handling of the potassium, the regulation
acting through diVerent receptors, have diVerent of renal ion transporters in hypokalaemia,
eVect on potassium deposition. â -stimulation and treatment of hypokalaemia and hy-
results in a shift of potassium into the cell, while perkalaemia will be discussed.
á-stimulation has the opposite eVect.3 The eVect (Postgrad Med J 2001;77:759–764)
of mineralocorticoids and parathyroid hormonein internal potassium homoeostasis is minimal at Keywords: hypokalaemia; hyperkalaemia; potassium best. In addition to these physiological regula-tors, internal potassium homoeostasis is also aVected by changes in acid-base and osmolarity.
Potassium is the most abundant cation in the Sudden changes in osmolarity, by shifting the body. It is predominantly restricted to the water out of cell, creates a solvent drag phenom- intracellular space, such that only 2% is located enon, and helps push potassium out of the cell, extracellularly and the remaining 98% is in the resulting in a rise in serum potassium (table 1).
intracellular compartment. The ratio of intra- The eVect of acid-base status is much more cellular to extracellular potassium (Ki/Ke) is complicated and depends on the nature of the the major determinant of resting membrane disorder (box 1). Although, the rule of thumb Yale University School
potential, and is regulated primarily by the has been that for each 0.1 unit change in pH, of Medicine, New
sodium-potassium ATPase pump located on there is a 0.6 mmol/l change in serum potas- the plasma membrane of most cells. Although sium, this is a very crude approximation and extracellular potassium accounts for only 2% varies greatly by the nature of acid-base of total body potassium, it has a major e Vect on disorders. For example organic acidosis as seen the ratio of Ki/Ke and through that on the rest- in diabetic ketoacidosis or lactic acidosis result ing membrane potential. As a result, serum in little or no change in serum potassium while potassium is normally regulated around the non-organic (mineral) acidosis, such as acidosis narrow range of 3.5–5.0 mmol/l.
of renal failure, has the greatest eVect. Other The daily intake of potassium in the western acid-base disorders shift potassium minimally.4 5 Correspondence to: diet is between 80–120 mmol. The kidney is Dr M Soleimani, Division of accounting for 90% of potassium loss daily.
Hypertension, University ofCincinnati Medical Center, The remaining 10% is excreted through the Box 1: EVect of acid-base disorders on
231 Albert Sabin Way, MSB gastrointestinal tract. The kidney is, therefore, 5502, Cincinnati, OH responsible for long term potassium homoeos- 45267–0585, USA x For any pH change the eVect of acidae- tasis, as well as the serum potassium concentra- mia is greater than alkalaemia.
tion. On short term basis, serum potassium is x Non-organic (mineral acidosis) results in Submitted 8 September also regulated by the shift of potassium a shift of 0.24–1.7 mmol/l per 0.1 unit pH Accepted 14 June 2001 between the intracellular and extracellular x Organic acidosis has little to no eVect on Regulators of potassium distribution between intracellular and extracellular potassium shift.
x Respiratory and metabolic alkalosis and Mechanism of action Potassium shift into cells respiratory acidosis result in similar small Activation of sodium-potassium shift of potassium into and out of cell respectively (0.1–0.4 mmol/l on average).
Activation of â receptors x In chronic acid-base disorders the final Activation of á receptors potassium reflects primarily the eVect on renal handling of potassium and to lesser Acid-base changes Exchange of H+ for K+ extent of transcellular shift.
Shifts potassium extracellularly Renal handling of potassium
Box 2: Classification of hyperkalaemia
mmol/day) is largely reabsorbed by proximal (1) Spurious hyperkalaemia nephron segments, including proximal convo- x Due to high platelet and/or leucocyte luted tubules and thick limb of Henle. The potassium that is excreted is, therefore, a result x Due to muscular activity during of secretion by distal segments, predominantly distal convoluted tubule and the collectingduct. Transport studies in these latter tubule (2) Transcellular shift of potassium x Acidaemia (for example, acute renal fail- segments have demonstrated that potassium secretion is accomplished via apical potassium x Hyperosmolality (for example, severe channels. The secretion of potassium in these nephron segments is indirectly but tightly cou- x â -blockers (for example, propranolol).
pled to sodium reabsorption via the amiloride- x Insulin deficiency (for example, type I sensitive sodium channel; increased sodium diabetes mellitus).
reabsorption increases whereas decreased so-dium reabsorption decreases potassium secre- (3) Increase intake tion. It is this secretory ability of the potassium x Infusion of potassium containing solu- channels in the distal segments which regulates the excretion of potassium. As a result, any x Increase potassium intake in patients with condition that decreases the activity of renal defect in potassium excretion.
potassium channels results in hyperkalaemia (4) Decrease renal excretion (for example, amiloride intake or aldosterone x Mineralocorticoid deficiency: (a) Addi- deficiency) whereas their increased activity son's disease, (b) isolated aldosterone results in hypokalaemia (for example, primary deficiency, (c) renin deficiency (for exam- aldosteronism or Liddle's syndrome).
ple, diabetic nephropathy), (d) angio- In summary, kidney is the major regulator of tensin II receptor blockers, (e) angio- long term potassium homoeostasis and serum tensin converting enzyme inhibitors, (f) potassium. However, on short term basis, insu- use of non-steroidal anti-inflammatory lin and catecholamines, among others, regulate serum potassium through changes in transcel- x Resistance to mineralocorticoids eVect: lular distribution of potassium.
(a) tubulointerstitial disease, (b) highdose mineralocorticoids antagonists (for example, spironolactone, trimethoprim).
Hyperkalaemia is defined as serum potassium x Severe renal failure.
greater than 5.0 mmol/l. True hyperkalaemiashould however be distinguished from pseudo-hyperkalaemia, a rise in serum potassiumsecondary to release of intracellular potassium metabolic acidosis; however, a sudden rise in during phlebotomy or storage of blood sample.
osmolality, especially in association with insu- During phlebotomy the combination of venous lin deficiency, could result in significant hyper- occlusions and hand clinching could result in kalaemia. â-blockers alone are rarely associated potassium release locally. If this is suspected, a with significant hyperkalaemia, however, they blood sample should be drawn from a free could play a contributory part.
flowing vein without fist clinching. Potassium Given the renal ability to excrete large can also be released in test tube by haemolysis, amount of potassium, increase in intake could severe thrombocytosis (usually >900 × 1010/l result in hyperkalaemia, only if associated with platelets) or leucocytosis (leucocytes >70 × 109/ subtle or overt defect in potassium excretion.
l). If this is suspected the measurement should Salt substitutes, which may contains as much be repeated using fresh heparinised blood drawn as 200 mmol of potassium per tablespoon, are carefully to prevent haemolysis.
major hidden sources of ingested potassium.
The incidence of hyperkalaemia in hospital- Hyperkalaemia can also occur by infusion of ised patients varies depending on the level of potassium containing solution at a rate that can potassium used from 1.4% to 10%. In the larg- not be handled by transcellular shift and/or est study in a single hospital overall incidence renal excretion (see below under treatment of of hyperkalaemia (defined as serum potassium hypokalaemia). The most important cause of >6.0 mmol/l) was 1.4%. Potassium supple- hyperkalaemia is, however, decrease in renal mentation and potassium-sparing diuretics potassium excretion. This is seen in many dis- account for about one third of the cases. Severe orders including mineralocorticoid deficiency, hyperkalaemia is more common in older such as Addison's disease or resistance to the patients with underlying renal insuYciency eVect of aldosterone such as seen in patients on treated with potassium supplementation. Hy- aldosterone antagonist drugs (box 2). Tri- methoprim, a commonly used antimicrobial 1:1000 deaths in hospitalised patients (re- drug, is an important cause of hyperkalaemia in viewed by Ponce et al6).
patients with mild renal failure.7 Although thisside eVect is more common on high dose intra- CLASSIFICATION OF HYPERKALAEMIA venous therapy, it does occur on regular oral Hyperkalaemia could be due to transcellular dose. Patients with renal failure can often shift, increase in intake, and/or decrease in out- maintain near normal serum potassium unless put (box 2). Transcellular shift is often due to glomerular filtration rate decreases below 15 Hypokalaemia and hyperkalaemia ml/min. However, a significant number of without a low renin level. In these patients we patients with renal disease have low aldoster- commonly do not embark on a costly and one levels with or without low renin level, or detailed evaluation and focus on long term have resistance to aldosterone eVect. This treatment. However in patients with normal group presents with mild to moderate renal renal function, and especially in patients failure and hyperkalaemia, often in association suspected of primary adrenal failure, a com- with renal tubular acidosis (type IV).8 plete work-up including measurement of aldos-terone and cortisol level is mandatory.
CLINICAL PRESENTATION One of the more overlooked and less well Hyperkalaemia is often asymptomatic and is understood causes of hyperkalaemia is the use discovered on routine laboratory tests. Patients of prostaglandin inhibitors or non-steroidal with severe hyperkalaemia (potassium >6.5 anti-inflamatory drugs (NSAIDS). Studies mmol/l) may, however, present with general- have shown that the use of NSAIDS, specifi- ised weakness, paralysis, and cardiac arrhyth- cally in conditions associated with raised basal mia, including cardiac stand still and sudden renal prostaglandins such as liver cirrhosis or death. In general, the severity of clinical mild renal insuYciency, can cause hyperkalae- presentation does correlate with the severity of mia by causing hypoaldosteronism. Two inde- hyperkalaemia. Changes in the electrocardio- pendent mechanisms are responsible for this gram (ECG) also reflect the severity of hyper- hyperkalaemia; first is the direct inhibition of kalaemia. In mild to moderate hyperkalaemia, renin synthesis by prostaglandin inhibition.11 changes in the ECG are subtle and often The second mechanism is indirect and is via limited to peaking of the T-wave. If hyperkalae- enhanced reabsorption of sodium and chloride mia is more severe, prolongation of PR and in the thick ascending limb which can result in QRS interval followed by loss of P wave and volume expansion and as a result suppress marked widening of QRS is seen. In extreme renin and aldosterone.11 hyperkalaemia, the ECG shows sine wave, If renal response to hyperkalaemia is appro- often followed by ventricular fibrillation. Al- priate (TTKG >5), increase in potassium though some patients show a gradual progres- intake, or transcellular shift of potassium sion of ECG findings, many progress rapidly should be suspected. As indicated above, tran- without warning. Therefore, hyperkalaemia in scellular shift most commonly occurs in the association with ECG changes is a true medical setting of metabolic acidosis, hyperosmolality, and/or insulin deficiency. If transcellular shift isruled out, hyperkalaemia is probably due to an WORK-UP OF HYPERKALAEMIA increase in potassium intake, which should be It is important to stress that in severe hyperka- established by a careful dietary (including food laemia diagnostic work-up should be post- supplements) and drug history.
poned until hyperkalaemia is treated. In otherpatients, if the cause of hyperkalaemia is notevident from the initial work-up, a stepwise MANAGEMENT OF HYPERKALAEMIA approach is recommended. The first step The initial management should be dictated by should be to evaluate the adequacy of the renal the changes in ECG. In the presence of ECG response to hyperkalaemia. Potassium excre- changes, hyperkalaemia should be considered tion is primarily through potassium secretion an emergency and treatment should begin in the cortical collecting duct. Urinary potas- immediately with calcium gluconate infusion.
sium concentration is however greatly aVected This should be followed by use of insulin and by the amount of water reabsorbed in the col- glucose or albuterol to help shift potassium into lecting duct. To evaluate adequacy of renal the cell before a more definitive treatment, response it is therefore important that urinary cation exchange resin (sodium or calcium potassium to serum potassium ratio be cor- polysteryene sulphone resin) and/or dialysis, is rected for urinary concentration. This is simply used to remove potassium from the body. Insu- done by dividing the ratio of urinary potassium lin and albuterol have an additive eVect in low- to serum potassium by the ratio of urinary ering serum potassium.12 Table 2 summarises osmolality to serum osmolality (urinary potas- emergency treatment for severe hyperkalaemia.
sium:serum potassium/urinary osmolality:se- Although sodium bicarbonate use has fallen rum osmolality). This ratio, referred to as tran- out of favour in patients on dialysis, it should stubular potassium gradient or TTKG, is >5 be considered in patients with significant and often 7 in hyperkalaemia and <1 in acidaemia where it is expected that infusion of hypokalaemia.9 10 It is worth mentioning that bicarbonate would increase serum pH signifi- the cut oV values of >5 or <1 are indicative of a cantly.13 Cation exchange resin mixed with sorbi- non-renal cause for high or low potassium, tol should be used orally if hyperkalaemia is not respectively. This formula, however, can not be life threatening, however resin mixed with used if urine is more dilute than the serum or water (and not sorbitol) can be repeated hourly contains very little sodium.9 10 for rapid removal of potassium. It should be The next step is to establish if low urinary remembered that each gram of sodium polysty- potassium excretion is due to low aldosterone or rene resin (Kayexalate) removes 0.5–1.0 mmol to resistance to aldosterone eVect by measuring of potassium in exchange for 2–3 mmol of serum aldosterone level. In patients with sodium. Therefore Kayexalate use is associated underlying renal disease hyperkalaemic renal with significant sodium infusion and can result tubular acidosis is a very common finding and in volume overload. In addition several cases of is often due to hypoaldosteronism with or colonic perforation have been reported in Treatment of hyperkalaemia Mechanism of action I. Membrane stabilisation 1–3 min/30–60 min Calcium gluconate 10% 10 ml iv II. Shift of potassium intracellularly 20 min/4–6 hours 10 U regular insulin iv with 50 ml 50% dextrose â -adrenergic agonist 20 min/2–4 hours Dose depending on the type of agonist used III. Removal of potassium Sodium or calcium polystyrene sulphone 1–2 hours/4–6 hours 15 g every six hours orally or 30–60 g by Immediate/duration of dialysis 2–3 hours haemodialysis iv = intravenous.
patients treated with Kayexalate mixed with loop diuretics) or in patients with gastro- intestinal diseases (diarrhoea). Thiazide and After the acute treatment of hyperkalaemia, a loop diuretics increase delivery of sodium to long term plan should be devised to prevent the collecting ducts, where it is reabsorbed via recurrence of hyperkalaemia. Initially the treat- the amiloride-sensitive sodium channel, there- ment should be directed toward correction of fore creating a favourable gradient for potas- the underlying cause of hyperkalaemia (such as sium secretion via potassium channels. In replacement therapy in patients with Addison's addition, volume depletion that results from disease). If hyperkalaemia is due to use of drug these diuretics increases aldosterone (by activa- (such as aldosterone antagonists or potassium tion of renin-angiotensin-aldosterone path- supplements), these should be discontinued. If way), further increasing potassium secretion hyperkalaemia is due to tubular defect in via the secretory potassium channels in the potassium secretion in association with renal collecting ducts. Increased aldosterone, in failure, several therapeutic manoeuvres should addition, can cause metabolic alkalosis by be considered including: increasing hydrogen mediated bicarbonate rea- x Hydration and volume expansion to increase bsorption in the collecting duct. This latter urine flow rate and sodium delivery to phenomenon can worsen the diuretic-induced exchange site.
hypokalaemia by increasing potssium shift into x Use of loop diuretics to increase sodium cells. The diuretic acetazolamide, which causes delivery and stimulate potassium excretion.
metabolic acidosis by decreasing bicarbonate x Restriction of dietary potassium intake to reabsorption in the proximal tubule, increases approximately 60 mmol/day.
potassium excretion by increasing the delivery x Use of oral mineralocorticoids such as of sodium and bicarbonate to the distal fludrocortisone in supraphysiological doses.
nephrons. Hypokalaemia can also be due by Most patients can be managed without use increased loss in the stool in patients taking of fludrocortisone, however in some patients large doses of laxatives or having diarrhoea.
use of this drug in doses of 0.4–1.0 mg Hypokalaemia due to potassium shift into cells is caused by medications, hormonaldysregulation, or raised blood pH.3 4 8 15 These oedema formation maybe a limiting side â -sympathomimetics eVects in use of this drug.
(that is brochodilators such as albuterol) orphosphodiesterase inhibitors (that is theophyl- line and caVeine), exogenous insulin and rarely Hypokalaemia is probably the most common calcium channel blockers. Decreased potas- electrolyte abnormality in hospitalised patients.
sium intake (less than 1 g/day), while rare, can It is usually defined as a serum potassium of lead to hypokalaemia. This is due to obligatory less than 3.5 mmol/l. Patients with mild potassium loss of 10–15 mmol/day by the kid- ney despite a low potassium intake.
mmol/l) usually have no symptoms. However, Among other disorders causing hypokalae- with more severe hypokalaemia (serum potas- mia magnesium depletion needs special em- sium of less than 2.5 mmol/l), generalised weakness can occur. In addition, patients with caused by either decreased dietary intake or increased loss, is a common electrolyte disor- necrosis (rhabdomyolysis) and paralysis. Both der in hospitalised patients. It can cause severe mild and severe hypokalaemia can increase the hypokalaemia by increasing renal potassium incidence of cardiac arrhythmias.
loss. The exact mechanism is, however, re-mains unclear. Hypokalaemia is also a com- CLASSIFICATION OF HYPOKALAEMIA mon finding in patients with raised serum Hypokalaemia can result from increased loss, aldosterone either secondary to the activation transcellular shift, or decreased intake of of the renin-angiotensin system (Bartter's syn- drome or Gitelman's syndrome) or due to (through the kidney or gastrointestinal tract) is overproduction by aldosterone-producing tu- the most common cause of hypokalaemia. Less mours (primary aldosteronism).
frequently, hypokalaemia can occur as a resultof shift of potassium from the extracellular CLINICAL PRESENTATION OF HYPOKALAEMIA space into cells. Rarely, hypokalaemia can Similar to hyperkalaemia, hypokalaemia is result from decreased intake of potassium.
often asymptomatic. This is specifically true in Increased potassium loss, which is the most patients with mild hypokalaemia (serum potas- common cause of hypokalaemia, occurs mostly sium 3.0–3.5 mmol/l). Patients with more in patients who are on diuretics (thiazide or severe hypokalaemia (serum potassium of less Hypokalaemia and hyperkalaemia than 2.5 mmol/l) usually present with general- caused by a potassium shift due to medication ised weakness and, in some cases, ascending or alkalaemia, however prolonged hypokalae- paralysis. In addition, severe hypokalaemia can mia is commonly due to renal or gastro- precipitate rhabdomyolysis which manifests as intestinal loss of potassium. The most common muscle tenderness and swelling. Cardiac ar- causes of hypokalaemia in clinical practice are rhythmias are common in hypokalaemia, spe- due to diuretics and gastrointestinal loss cifically in patients with underlying heart secondary to diarrhoea and/or vomiting. These disease or on digoxin. In moderate to severe aetiologies should therefore be considered first hypokalaemia changes in ECG are minimal before exhaustive and sophisticated work-up is and is often limited to the presence of a U initiated. In other patients the initial step is to see if hypokalaemia is in association withsystemic hypertension or not. In the former RENAL SYNDROMES ASSOCIATED WITH group hypokalaemia is associated with a high mineralocorticoid eVect due to high aldoster- In addition to the above clinical symptoms, one (as in primary aldosteronoma or renal hypokalaemia can cause several distinct renal artery stenosis) or cortisol as in Cushing's dis- syndromes as will be discussed below.
ease or hyperactive sodium channel as inLiddle's syndrome. Measurement of the renin, Nephrogenic diabetes insipidus aldosterone, and cortisol concentrations under Hypokalaemia can impair urinary concentrat- appropriate conditions would help in diVeren- ing mechanism and result in nephrogenic tiating among these aetiologies. In normoten- diabetes insipidus. Patients with nephrogenic sive patients, hypokalaemia could be secondary diabetes insipidus due to hypokalaemia present to overt or occult gastrointestinal loss or due to with polyuria and polydipsia. Molecular stud- renal potassium wasting. Although low urinary ies have demonstrated that potassium deple- potassium (less than 15 mmol/l) would favour tion causes downregulation of the water chan- gastrointestinal loss, high urinary potassium is seen in patients with vomiting or diarrhoea due therefore impairing the renal concentrating to secondary elevation in the aldosterone level mechanism and resulting in polyuria.16 and is therefore not very helpful. In normoten-sive patients with renal potassium wasting, a low serum bicarbonate would favour the diag- Hypokalaemia can contribute to the mainte- nosis of renal tubular acidosis, while a high nance of metabolic alkalosis in several disease serum bicarbonate is compatible with the high states (such as vomiting) by enhancing bicar- mineralocorticoid eVect seen in patients with bonate absorbing ability of renal tubules.17–20 Bartter's or Gitelman's syndromes. Magne- This in turn decreases the ability of the kidney sium deficiency can result in renal potassium to excrete the excess bicarbonate and as a result wasting and is often seen in alcoholics who are maintains the plasma bicarbonate at a raised also nutritionally depleted. Diuretic and/or level.17 Functional and molecular studies in laxative abuse often mimics these rare syn- luminal and basolateral membranes of kidney dromes and should be considered in any adult proximal tubules and in microperfused kidney patient with hypokalaemia of unknown aeti- nephrons have demonstrated that hypokalae- ology and ruled out by urinary test for specific mia upregulates the expression of bicarbonate diuretics and stool test for phenolphthalein.
absorbing transporters in proximal tubules andcortical and medullary collecting ducts.17–20 MANAGEMENT OF HYPOKALAEMIA There is also evidence in support of hypokalae- The management of hypokalaemia is almost mia being involved in the generation of always by potassium replacement, with the metabolic alkalosis in human by increasing amount of potassium supplement depending on the severity of hypokalaemia (box 4). Thepotassium can be given orally (in mild to Enhanced renal chloride excretion moerate hypokalaemia) or intravenously (in Hypokalaemia increases urinary chloride ex- severe hypokalaemia). When given intrave- cretion.19 20 Functional and molecular studies nously, the rate of potassium administration in the kidney have demonstrated that renal should not exceed 20 mmol/hour. To calculate chloride wasting in hypokalaemia is due to the amount of potassium supplement, one suppression of the apical sodium-potassium- should have an estimate of the potassium defi- chloride cotransporter in the thick limb of cit. On average, a reduction of serum potas- Henle and the apical sodium-chloride cotrans- sium by 0.3 mmol/l suggests a total body defi- porter in the distal convoluted tubule.21 It is cit of 100 mmol. Based on this formula, a possible that by increasing renal chloride patient with a serum potassium of 2.6 mmol/l excretion, hypokalaemia can result in hypo- needs at least 300 mmol of potassium for the chloraemia, which in turn can contribute to the correction of the deficit. In calculating the total maintenance of metabolic alkalosis in patho- body potassium deficit one has to consider fac- physiological states.17 tors that can independently aVect serumpotassium. A patient with a serum potassium of WORK-UP OF HYPOKALAEMIA 2.6 mmol/l has less total body deficit at blood In working up patients with hypokalaemia a pH of 7.5 than 7.3. The reason is that alkaline combination of common sense as well as serum pH (that is, 7.5) can independently pathophysiology should be used (box 3). Tran- lower the serum potassium by intracellular sient short term hypokalaemia is usually potassium phosphate and potassium bicarbo- Box 3: Work-up of hypokalaemia
nate can be used in certain conditions. Potas-sium phosphate can be used in patients with (1) Acute hypokalaemia (less than 12 hours of combined potassium and phosphate depletion x Alkalosis (metabolic or respiratory).
(for example in patients with liver cirrhosis or x Insulin therapy (for example, in severe diabetic ketoacidosis). Potassium bicarbonate can be used in patients with potassium depletion x â -stimulant (for example, albuterol).
and metabolic acidosis (for example in distalrenal tubular acidosis). Aside from intravenous (2) Chronic hypokalaemia (more than 24hours of onset) potassium chloride for severe hypokalaemia, x With normal blood pressure.
mild or moderate hypokalaemia (see above) can be treated with oral potassium chloride. Usually, gastrointestinal tract: (i) diarrhoea, (ii) laxa- 50 to 100 mmol of potassium chloride is required per day to maintain serum potassium (B) Increased potassium loss through kid- concentration within the normal range in ney: (i) diuretics, (ii) hypomagnesaemia, patients with increased potassium loss (that is, in (iii) renal tubular acidosis (proximal and patients receiving a diuretic).
distal), (iv) genetic defects (for example,Bartter's syndrome, Gitelman's syndrome).
1 Rosa RM, Williams ME, Epstein FH. Extrarenal potassium x With high blood pressure.
metabolism. In: Seldin DW, Giebisch G, eds. The kidney, (A) Increased aldosterone: (i) primary physiology and pathophysiology. New York: Raven, 1992:2165–90.
aldosteronism (low renin), (ii) renal artery 2 DeFronzo RA, Felig P, Ferrannini E, et al. EVect of graded stenosis (high renin), (iii) Cushing's disease doses of insulin on splanchnic and peripheral potassium (high renin).
metabolism in man. Am J Physiol 1980;238:E421–7.
3 Brown MJ, Brown DC, Murphy MB. Hypokalemia from (B) Normal or low aldosterone: (i) hyperac- beta-2 receptor stimulation by circulating epinephrine. N tive sodium channel (Liddle's syndrome), Engl J Med 1983;309:1414–19.
4 Androgue HJ, Madias NE. Changes in plasma potassium (ii) increased liquorice intake.
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5 Fulop M. Serum potassium in lactic and keto acidosis. N Engl J Med 1979; 300:1087–90.
6 Ponce SP, Jennings AE, Madias NE, et al. Drug-induced Box 4: Treatment of hypokalaemia
7 Velazquez H, Perazella MA, Wright FS, et al. Renal (1) Intravenous potassium (as potassium mechanism of trimethoprim-induced hyperkalemia. Ann
Intern Med
8 Dubose TD Jr. Hyperkalemic hyperchloremic metabolic x Usually reserved for severe hypokalaemia acidosis: pathophysiologic insight. Kidney Int 1997;51:591–
(serum potassium of <2.6 mmol/l).
9 Ethier JH, Kamel KS, Magner PO, et al. The transtubular x The rate of should not exceed 20 potassium concentration in patients with hypokalemia and hyperkalemia. Am J Kidney Dis 1990;15:309–15.
10 Kamel KS, Quaggin S, Scheich A, et al. Disorders of potas- (2) Oral potassium sium homeostasis: an approach based on pathophysiology.
x Potassium chloride: 40–100 mmol/day in Am J Kidney Dis 1994;24:597–613.
11 Wright FS, Giebisch G. Regulation of potassium excretion.
divided doses.
In: Seldin DW, Giebisch G, eds. The kidney: physiology and x Potassium phosphate (in patients with pathophysiology. 2nd Ed. New York: Raven Press, 1992: hypokalaemia and hypophsphataemia).
12 Allon M, Copkney C. Albuterol and insulin for treatment of x Potassium bicarbonate (in patients with hyperkalemia in hemodialysis patients. Kidney Int 1990;38:
13 Blumberg A, Weidman P, Shaw S, et al. EVect of various therapeutic approaches on plasma potassium and major
regulating factors in terminal renal failure. Am J Med 1988;
14 Rashid A, Hamilton SR. Necrosis of gastrointestinal tract in Box 5: Selected bibliography
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potassium and acid-base metabolism in 15 Gennari FJ. Hypokalemia. N Engl J Med 1998;339:451–7.
association with renal disease. In: Schrier 16 Amlal H, Krane CM, Chen QK, et al. Early polyuria and urinary concentrating defect in potassium deprivation. Am J RW, Gottschalk CW, eds. Diseases of the kidney. 6th Ed. Boston: Little, Brown, 17 Alpern RJ, Emmett M, Seldin DW. Metabolic alkalosis. In: Seldin DW, Giebisch G, eds. The kidney: physiology and patho- 1997: 2452–77.
physiology. 2nd Ed. New York: Raven Press, 1992: 2733–56.
x Halperin M, Kamel KS. Potassium. Lan- 18 Soleimani M, Bergman JA, Hosford MA, et al. Potassium depletion increases Na+:CO =:HCO - cotransport in rat renal cortex. J Clin Invest 1990;86:1076–83.
x Gennari FJ. Hypokalemia. N Engl J Med 19 Amlal H, Habo K, Soleimani M. Potassium depletion upregulates the expression of the renal basolateral Na+:HCO - cotransporter (NBC-1). Am J Physiol 2000;279:F532–43.
20 Silver R, Soleimani M. H+-K+-ATPases: regulation and role in pathophysiologic states. Am J Physiol 1999;276:F799–811.
In addition to potassium chloride, which is 21 Amlal H, Wang Z, Soleimani M. Potassium depletion downregulates chloride-absorbing transporters in rat kid- commonly used in treating hypokalaemias, ney. J Clin Invest 1998;101:1045–54.
Postgrad Med J 2002;78:124–126 toxic agents. These diseases are sometimes Department of Medicine, Community Health Center, inaccurately referred to as "food poisoning", Mannadipet, Pondicherry 605 501, India; and they represent one of the most wide- Prakram@md4 vsnl.net.in The role of tricyclic spread and overwhelming public health prob-lems of the modern world. Infants, children, antidepressants and tramadol in Department of Clinical Pharmacology, Jawaharlal the elderly, and the immunocompromised are Institute of Postgraduate Medical Education and more commonly affected.1 Infection of six Research, Pondicherry 605 006, India members of a family is described here.
We read with interest the review article on The head of a family (61 years), his wife (59 alternative opioids to morphine in palliative years), their son (38 years), daughter in law care.1 The author has mentioned in detail 1 Barnett M. Alternative opioids to morphine in various factors—biomedical, genetic, and palliative care: a review of current practice (35 years), and two male grandchildren (14 psychological—which influence the effect of and evidence. Postgrad Med J and 11 years respectively) were admitted to opioids. Though most of the aspects are well hospital with gastroenteritis. About four 2 Gloth III FM. Geriatric pain. Factors that limit covered, the role of depression has not been hours earlier they had consumed pieces of pain relief and increase complications.
discussed, and this has a tremendous impact freshly cut watermelon. During the past seven on the manifestation and management of days they had consumed home cooked food 3 Hardy PA. Analgesics. In: Hardy PA, ed.
pain.2 Initial control of depression greatly Chronic pain management: the essentials.
and clear water from the domestic supply. The London: Greenwich Medical Media, 1977: head of the family, who had received the lion's must be treated aggressively (for example share of the fruit, was affected the most and with antidepressants and psychotherapy ses- 4 Salemo E. Analgesics. In: Salemo E, ed.
was in a state of shock and acute renal failure.
Pharmacology for health professionals. USA: sions) or pain management will remain It took three days for his urinary output and Mosby, 1999: 124–53.
elusive. It has also been shown that in renal parameters to improve. He was treated 5 Bamigbade JA, Langford RM. Tramadol patients who are taking opioid drugs, the bio- hydrochloride: an overview of current use.
with intravenous fluids, ciprofloxacin, metro- availability of opioids is increased with anti- Hospital Medicine 1998;59:373–6.
nidazole, and other conservative measures for depressants; the tricyclic drugs are membrane five days. Other members of the family had an stabilising, which may account for the early uneventful stay in the hospital and were onset of action in patients with chronic pain.3 discharged on the second day after admission.
The author mentioned the advantages of The daughter in law, who had received the transdermal administration of fentanyl. She First, I would like to address the apparent smallest share of the fruit, was affected the noted that it is highly acceptable to patients omission of a discussion of depression. I am least and had just two or three loose stools in and the patches can be applied by patients or entirely in agreement with the respondents' hospital. Haematology, urinalysis, and chest relatives themselves. We would like to stress comments that depression has a major role in radiography of all the family members were that 25% to 50% of patients above the age of the manifestation and management of pain.
normal. Blood biochemistry of the head of the 65 suffer from major pain problems. Age However, in this review I was considering the family suggested uraemia and acidosis. Stool related changes in skin integrity, subcutan- differential factors influencing choice of cultures of all members of the family grew an eous fat, and water content can affect patient opioid, not the assessment of pain per se. I enteroinvasive variety of Escherichia coli, which response to transdermal products. In fact, pointed out at the outset that cancer pain was was non-motile with non-lactose ferments.
fentanyl patches have been associated with multifactorial, and that a thorough assess- We asked the fruit seller about the purchase death in opioid-naive older adults in doses as ment was a prerequisite to successful man- of watermelon and this revealed the fact that low as 50 µg/hour.2 Also, serum fentanyl con- agement, but that the review was of strong watermelons can be made more colourful and centrations may increase by one third in opioids, and was beginning from the point at sweet without cutting them open. Instead a patients with a body temperature of 40oC or which these were considered appropriate long needle, into the core, can inject sweet- more. It has been suggested that fentanyl treatment. I did include the effect of antide- ener and colouring agents, three to four hours should not be given to children younger than pressants in enhancing bioavailability of before sale. The nature of the injected agents 12 years of age or to patients younger than 18 opioids in the text and in table 5, but in the was not revealed by the fruit seller for obvious years of age who weigh less than 50 kg. Addi- context of drug interactions.
reasons. Culture from the solution that had tionally, fentanyl has a long duration of action With regard to transdermal fentanyl: the been injected (which had been prepared and (up to 72 hours) and therefore the side effects authors appear to imply that in beginning stored in an earthenware bowl), also grew and adverse reactions are not easily reversed.4 with a discussion of its advantages, I was multiple colonies of the enteroinvasive variety In view of this, we believe that transdermal advocating liberal use of this drug and route. I of E coli, which were biochemically lactose fentanyl should not be used liberally.
went on to describe all its disadvantages, positive, non-motile, with non-lactose fer- It was also stated by the author that trama- including its interpatient variability and long dol is less potent than morphine and less duration of action causing potential problems Diarrhoeal diseases have been commonly effective for managing severe pain. However, of overdose. I was attempting to provide a bal- attributed to a pathogen contaminated water tramadol has been used extensively and anced overview of a drug that has proved very supply, but it is now recognised that food also evaluated over the last 20 years. It has proved popular with patients and health profession- plays an equally important part in 70% of as effective as the strong opioids in acute and als while cautioning on its overuse.
such illnesses. Besides the usual foods, con- chronic pain settings. In particular, tramadol On the question of tramadol, I do not tamination has been reported in other foods administration results in little respiratory dispute that it is an effective analgesic and has such as raw fish, shellfish, bivalve molluscs depression in comparison with equianalgesic a broad spectrum of clinical use. However, (oysters, cockles, mussels), raw shrimp, pork, both from personal practice and my review of doses of opioids, such as morphine or mixed d'oeuvre, crabs, prawns, rock lobster, literature pertinent to palliative care, I con- pethidine. Tramadol has a long record of effi- cooked squid, turkey, street foods, eggs, egg cluded that its efficacy in the management of cacy and safety, and although it should be salad, cold asparagus, aquatic plants, bottle progressive severe cancer pain is less conclu- avoided or used with caution in epileptic feeds (for infants), ice creams, chocolates, sively demonstrated, and thus questioned its patients, it is now the fourth most commonly candies, etc. The chief contaminants are role in palliative care. Respiratory depression prescribed analgesic worldwide.5 It is cer- bacteria (E coli, shigella, salmonella, Vibrio is rarely an issue in palliative care, nor opioid tainly useful in the treatment of chronic, non- cholera 01, Campylobacter jejuni, brucella, Bacil- abuse, although I accept that low abuse malignant, and malignant pain syndromes.
lus cereus, Staphylococcus aureus, Clostridium perf- potential may facilitate adequate analgesic Another considerable advantage of tramadol prescribing in chronic non-malignant pain.
is its very low abuse potential. Consequently, helminthes (Trichinella spiralis, Taenia saginata, it is not deemed a controlled (scheduled) Taenia solium, clonorchis, Fasciola opisthorchis, Watermelon poisoning Paragonimus spp), protozoa (Entamoeba hysto- In view of the above, we believe that trama- litica, Giardia lamblia, Cryptosporidium spp), and dol has an important role as an alternative Food borne diseases are a result of ingestion enteric viruses (rotavirus hepatitis A&E virus) opioid to morphine in palliative care.
of foods contaminated by either infectious or Infections due to pathogenic strains of E coli There is evidence of tight editing in terms of sharp, and relevant photographs and illustra- are probably the commonest cause of diar- chapter style and layout and excellent cross tions are an added bonus and the tables such rhoea in developing countries. The contami- referencing between the chapters. The book is as those of causes of vaginal discharge and nation of food with micro-organisms is enlivened by quotations in wide easy-on-the- genital ulceration are exemplary in their clar- eye margins. These also host simple line ity and comprehensiveness. Relevant aspects • Use of contaminated equipment.
drawings of such important practical aspects of dermatology and even psychiatry are briefly of teaching as the ideal distribution of teacher considered where appropriate.
• Infected food handlers.
and taught round a bed. The advice to ensure Three opening chapters on aetiology of • Use of raw and contaminated ingredients.
students do not go off on electives to countries STIs, taking a sexual history and counselling with military or civil unrest is not profound approaches, are followed by chapters dealing but well timed. Each chapter provides sugges- with STIs causes by bacterial, viral, and other • Addition of toxic chemicals or use of foods tions for further reading.
organisms in turn. For once a correct balance containing natural toxicants like mush- The principles and examples are, as the edi- (in terms of their respective incidence in the tors suggest, relevant to postgraduate medical UK) is shown between coverage of HIV and Gastroenteritis by Salmonella javiana con- education and other healthcare professionals.
non-HIV STIs. Other chapters are problem tamination of watermelon has been described But for those involved in the teaching of oriented and consider such commonly pre- in 26 cases in the USA.2 Contamination of medical students, this book from Dundee, a senting conditions as urethritis and pelvic fruit by such a novel method as described here teaching centre of excellence, is warmly inflammatory disease. Comprehensive treat- may prove to be a major public health hazard, recommended for those who want to improve ment guidelines for both the UK and USA and hence is noteworthy.
their understanding and performance and conclude the book.
hence enjoyment of this Hippocratic responsi- As STIs continue to rise in the UK, this text T K Pande, A H Khan, R Pipersania, will prove an indispensable ready reference S K Sethi, Y Rath guide for paediatricians, physicians, GPs, Department of Internal Medicine, J L N Hospital gynaecologists, dermatologists, and surgeons.
and Research Center, Bhilai 490 009, India; Fellowship of Postgraduate Medicine, I will add my copy to the other three essential reference books on my surgery desk.
Making Sense of Statistics and 1 World Health Organization. Food borne General Practitioner, disease: a global health and economic Merton Park, London, UK problem. Food borne disease: a focus forhealth education. Geneva, Switzerland: By Anna Hart. (Pp 162; £19.95.) Radcliffe WHO, 2000: 1–34.
Medical Press, 2001. ISBN 1-85775-472- 400 MCQs in Paediatrics for 2 Blostein J. An outbreak of Salmonella javiana MRCPCH Part I.
associated with consumption of watermelon.
Journal of Environmental Health This book describes the essentials of statistics By Nagi G Barakat. (Pp 212; £14.95.) Royal and data presentation. The first chapters deal Society of Medicine Press, 2001. ISBN with the different types of study designs, the various forms of data and the characteristicsof pictorial forms of presenting data. Subse- This paperback book in fact has 463 questions quent chapters deal with distributions, means including a 60 question examination. The for- and medians, and measures of variability. The mat is of MCQs as used in the part I of the author describes confidence intervals, p MRCPCH examination and the question values, statistical power, and type I and II material does cover the full syllabus for this.
The reviewers have been asked to rate these errors. The final sections are on confounders, The answers provide some explanations for books in terms of four items: readability, how interactions, measures of correlation, hierar- the questions but not all. The evidence for the up to date they are, accuracy and reliability, chy of evidence, causality, and how to assess answers isn't related to specific text. However, and value for money, using simple four point papers. The author describes the terms used in there are a number of recommended texts and scales. From their opinions we have derived evidence based medicine such as absolute references listed, but at least one of these an overall "star" rating: * = poor, ** = reason- risks and the number needed to treat. A glos- texts, that for neonatology, does not show the able, *** = good, **** = excellent.
sary of terms used is contained in the appen- most recent edition edited by Roberton and The book will be of invaluable use for those As with all MCQ questions, some of the A Practical Guide for Medical just starting a research career or in its early answers are arguable but there are certain stages. It is comprehensive and clearly written answers given that are clearly completely with many illustrative examples. The text wrong, which will further mislead the exam- Edited by John A Dent and Ronald M Harden.
covers well all the areas that are of interest to ination candidate.
(Pp 453; £34.95.) Churchill Livingstone, Although the material covers the syllabus, 2001. ISBN 0-443-06273-0.**** projects. The pitfalls of different tests are well the questions that have been prepared do not described and the book is competitively reflect the quality of the questions expected in This book tells you all you wanted to know the membership examination.
and a good deal more that you now need to Given the thirst for examination questions know about the revolution that has been tak- among membership candidates, however, it is ing place in undergraduate medical education likely that some candidates will find the book West Norwich Hospital, UK in the past decade or more. The editors' stated useful in their preparation.
intention is to provide jargon-free under- standing of contemporary educational princi- Fast Facts—Sexually Transmitted ples and provide practical advice on dealing Leicester General Hospital, with all aspects of teaching. They succeed and Examination Committee, brilliantly well.
By Ann Edwards, Jackie Sherrard, and Royal College of Paediatrics and Child Health, UK The book is divided into seven sections Jonathan Zenilman. (Pp 104; £12.00.) Health (totalling 39 chapters in all) starting with Press, 2001. ISBN 1-899541-04-7.**** aspects of the curriculum, learning situations Imaging Picture Tests for the such as lectures, small groups, wards, primary In a month when all GPs in my area have been care etc, educational strategies (independent, notified of an epidemic of syphilis in London, the publication of this book could not be more By A P Winrow. (Pp 205; £19.95.) Churchill professional), aids such as computers, audio- video, and guides, themes (basic sciences, There has long been a need for a concise, communication skills, ethics, informatics etc), affordable, accessible, and accurate textbook means of assessment, and aspects of students on sexually transmitted infections (STIs) for This is a useful paediatric teaching book for and staff such as selection, support staff non-specialists in genitourinary medicine and candidates studying for the MRCPCH final development, and course monitoring.
this volume fills the gap perfectly. The clear, examination. It may also be useful for candidates for the Diploma for Child Health.
020-7288-3134, email: k.stephens@chime.
It contains a selection of 100 varied paediatric and neonatal cases of the types commonlyseen in the examination. There is an easily Fellowship of Postgraduate accessible question and answer format on the 25 April 2002—History of herbals, a talk by following page with useful comments rel- Medicine & CHIME, Royal Free & Bruce Madge of the British Library.
evant to the condition being demonstrated.
University College Medical There are also useful examination tips applied 11 May 2002—Use and abuse: a history of to each case.
opium, University of Leeds Medical History The author admits that some of the images Clinical Governance, Thursday, 21 were obtained from copy film and as a result For further information contact the Thackray some of the images are perhaps not as clear as Museum, Beckett Street, Leeds LS9 7LN (tel: they might have been. However, the examina- A one day conference for doctors wishing to 0113 244 4343, fax: 0113 247 0219, email: tion candidate with the help of the answers become more involved in clinical governance info@thackraymuseum.org, web site: thack and comments should be able to follow the at the Commonwealth Conference Centre, Kensington High Street, London.
The examination candidates will find this a PACES (MRCP) Part II useful additional text to assist their learning.
It could also provide useful CPD for self Two two day courses designed as final assessment by already qualified paediatri- preparation for the PACES examination to be cians in addition.
held at the Whittington Hospital, London.
Communication Skills and Ethics: 7 and 8 February 2002. Cost: £500.
An error occurred in the above paper, pub- Leicester General Hospital, Clinical: 12 and 13 February 2002. Cost: £500.
lished in the December issue of the journal and Examination Committee, For details contact Kate Stephens, CHIME, (2001;77:759–64). The name of the first
Royal College of Paediatrics 4th Floor Holborn Union Building, Archway author was spelt incorrectly; the correct spell- and Child Health, UK Campus, Highgate Hill, London N19 3UA (tel: ing is A Rastegar.
Hypokalaemia and hyperkalaemia
A Rastergar and M Soleimani 2001 77: 759-764 Postgrad Med Jdoi: 10.1136/pmj.77.914.759 Updated information and services can be found at: These include: This article cites 16 articles, 3 of which can be accessed free at: Article cited in: Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
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Volume 20 • Number 2 March - April 2006 President Report from the Hill Submits 2007 As we reported in our last nel. As a result, patients were forced to Advocate, the Department of use the more expensive private sector VA Budget Defense has proposed signifi- medical providers. One part of the

An effective approach to smoking cessation

Smoking Cessation Developed By: Carolyn Whiskin, RPh, BScPhm, NCMP Educational Grant Provided By: UCB Canada Inc. March 2013  The information contained in this presentation is for educational purposes only and is not intended to replace the advice of your health care provider.  Always consult your physician before starting any new program At the end of this session, you will: