LasoraroRy Electrolytes and acid-base: common fluid and electrolyte disorders Glovambattista Capasso Robert Unwin Abstract Disturbances of fuld and electrolyte balance are common in cnical prac: tice, especially na hospital setting, and maybe latogeni or compounded by inappropriate mecca or surgical treatment. Ther recognition and appropriate management are not necessarily cific or comple; while spec formulae and standard protocols can be eof atthe bedside, there is no substitute for an undestancng, ané apalication, of some basic principles of renal and endocrine physiology, which Is what this Ace tes to provide, Keywords acid-base; nephron structure; potassium: sodium; water balence Knowledge of basic renal physiology (including transport func- tion along the nephron and its regulation) is useful, because it rakes it easier to work through and understand most clinical disorders of fluid and electrolyte balance. Unfortunately, patients seldom present with a single acid-base or fluid and electrolyte disturbance, so the real challenge isto determine which disorder ‘came first, before rushing in and treating in isolation what may seem to be the major clinical abnormality. First, we need to con sider the main homeostatic functions of the kidney and, more specifically, the essential workings of its functional unit, the nephron (glomerulus and renal tubule) The nephron (Figure 1) ‘The amount of filtration atthe glomerulus (~180 lires/day with a normal glomerular filtration rate (GFR) of 128 ml/min) Is so large that the renal tubule is concerned principally with reabsorption, though itis also involved in the secretion of a few ions (H™ and K*), and other solutes like weak organic acids and bases (including some drugs or metabolites). Most of the reabsorptive (iransport) processes occur inthe proximal (convoluted ~ pars convoluta) tubule and the loop of Henle (LOH). However, the different parts of the distal tubule and collecting duct have an Giovobetiste Cepasso nor is Professor of Nephrology ot the ‘Second Univesity of Naples, Naples, aly. Competing interests: none eclored. Robert Unwin eo rn is Professor of Nephrology and Physiology at University College London, Ux, and Honorary Consultant Nephroiogist atthe Roya Free Hospital Competing inarests: none dectared 368 or persue us nly No ber ase without permission, STGATIONS important role in determining the final urinary excretion of Key fons (eg. Na’, K and H”), and also of water.! Table 1 sum- rmarizes the relative (to their filtered load) amounts of the main solutes reabsorbed in the proximal tubule. The LOH, which com- prises the proximal straight tubule (pars recta) thin descending limb, and the thin and thick ascending limbs, is responsible for the reabsorption of ‘an additional ~40% of filtered Na” 45% of filtered C~ ~45% of filtered K* ~25% of filtered water {important quantities of Ca!* and Mgi* In the distal tubule and along the collecting duct, reabsorption of Na? and Cl- continues, and their inal urinary excretion is usually <1% of what is fitezed (known as fractional excretion) whereas net secretion of K* and H* occurs in these nephron segments. (Some Ca‘* reabsorption also takes place in the distal tubule.) Water reabsorption in te distal nephron varies, depend Ing on the level of circulating vasopressin (AVP; antidiuretic hormone, ADH), which is determined by plasma osmolality and extracellular fluid volume (ECFV) status. ‘Most of the transport processes taking place along the renal ‘tubule are coupled directly or indirectly to the reabsorption of [Na*: it passively enters te lining epithelial cells from the lumen (fltrate) across the apical cell membrane and down its con- centration (strily, its electrochemical) gradient via a series of transporters (co-transporters and exchangers) or Na channels; its exit across the basolateral membrane requires the ‘sodium pump’ (Na*/K*-ATPase), which is ultimately responsible for ‘most of the reabsorptive and secretory processes (except for a few other pumps wansporting H”, C3!" and H*/K* exchange that are also energy-requiting ATPases) along the renal tubule Indeed, the mechanism of Na* reabsorption is essentially the same throughout the tubule; only the route of entry into the cell, is different from one segment to another* Since Na i the domi rant extracellular cation and, therefore, the main determinant of osmolality in the ECFV, and thus water distribution between extracellular and intracellular uid compartments, its balance is critically important in maintaining the ciculating volume (which is part of the ECPV) and arterial blood pressure (BP). Hence, ‘many of the extsinsi regulators of renal function are intended to alter Na* excretion and to preserve sodium balance.? ‘The main extrarenal Na‘-controling mechanisms ‘© Aldosterone - the major regulator of Na* reabsorption (and K* and H* secretion) in the distal nephron is aldosterone, secreted by the zona glomerulosa of the adrenal cortex in response to raised plasma angiotensin II levels or high plasma [IK]. Aldosterone stimulates the sodium pump and the apical Na* channel (the epithelial sodium channel, ENaC) of prin- cipal cells; this increases electrogenic Na“ reabsorption, Which depolarizes the apical membrane and faciltates K" secretion by these cells (as well as H” secretion by adjacent, acid-serotng, intercalated cel). “Atrial natriuretic peptide is released from the cardiae atria in response to stretch; it increases Na* excretion by suppressing the renin-angiotensin-aldasterone system, and directly inhib- hing Na* reabsorption inthe (medullary) collecting duc, eepyighSI0Te issn iae Arp mse‘wsoeaon Transport of water and sodium along the nephron Distal convoluted tubule i Nadie | et oo o B ccteinss Non t Ke 4,0 180 ttres/day om 2% Ban ‘Na* 26,000 mmol/day ie a 7 ints 4 a secre i rene , z ue nis fie Figure 1 A diagram of a nephron sacs u Seema sae er ae semen Sao ee ~ reabsorption offitered H,0 ‘CH,0 (maximal ute urine, <100 mOsmal/kg)~ 20 tes + Vasopressin ~ in addition to its key role in water handling, vasopressin increases urea reabsorption in the medullary col Jecting duct, and it may also have a significant stimulatory effect on Na* reabsorption inthis nephron segment ‘+ Angiotensin 1 and sympathetic nerve (noradrenaline) stimulation both increase Na* reabsorption, mainly in the proximal tubule, but they also reduce GFR * Other factors that act locally (paracrine) may also influence \Na* reabsorption; they include endothelin, bradykinin, and nitric oxide and ATP, which al seem to inhibit Na* reabsorp- tion along the collecting duct, The proximal tubule ‘The proximal convoluted tubule (the intl 2/3 ofthe proximal tubule ~ see Figure 1) reabsors: + slucose (-100% ofthe tered ose) + amino acids (100%) + low molecular weight proteins (.. retinol binding protein and some normally tered albumin) (-100%) sodium (-50%) chore (4589) potasslum (45%) 1,0 30%) Diearbonate (80%) Phosphate (-80%) {alcium 50%) magnesium (15%) urea (48%) urate (-90%) Tablet 146 mmol/l) means water loss or sodium gain, but {tis usually due to water loss or a failure to drink enough, and cells are therefore shrunken, Figure 3 summarizes the main body fluid compartments and their relaive volumes; ¢indieates that water ean move freely between them, determined only by any differences in osmolality. As already mentioned, since Na* is the major cation in the ECFV it will determine ECFY osmolality ‘and govern fluid shifts between the ECFV, and the intracellular fluid volume (ICFV); i is therefore an index of total body fluid (TBF) osmolality. Note also that musele Is an important ‘sump’ for body water and that a low muscle mass, particularly in (elderly) women, predisposes to water overload! and dlilutional hyponatraemia.* Hyponatraemia Almost all hyponatraemia is diltional and plasma osmolality (oxn) is low; it indicates that water intake execeds the renal capacity to excrete it, Upto 3% of hospital inpatients are reported to have significant hyponatraemia and this corelates with their mortality. The presence of hyponatraemia, however, is only 2 reflection of the seriousness of any underlying ilness, such as severe heart failure or liver disease, Na“ loss may transientty lower Py, (and therefore Poy, but water excretion by the Kid- ‘eys will normally correct this. With normal glomerular filtration ‘nd proximal reabsorption, and in the absence of vasopressin, ‘The mechanisms of acidification in the proximal tubule and collecting duct Urine Glutanine Bs o-ketogitarate ane Y he 2Hco, Proximal tubule elt [NNE, sodium hydrogen exchanger, the maln mechanism for apical bicarbonat anfiydrae type 4, the sofom ofthe enzyme carbone antyrase (wtch ata eintercalatea cet Ea ane intercalated cell re and sodium reabsorption along the proximal tubule; CAV, carbonic lyse the conversion of carbon dloxide and water to carbonic acid and thusto bicarbonate and hydrogen fn) present in the brush border membrane ofthe proximal tubule ony; Cl carbon aniydrase type 2, the Intracellar form of arboni anhyase presen in bat the proximal tubule igure 2 enone 357 370 Devnet Cay com at ar or pon ney occ ou person and collecting duct. pag HT. Essa Al pete‘AODRATORY INVESTIGATIONS Reduced, increased and normal effective arterial blood volume (EABV) in hyponatraemia cna Reduced (with oedeme) Cardiac flue, hepatic falure and the nephrotic syndrome = low spot Uy ised plasma urate ond uree vals relative to eeatinine suggest renal hypoperfusion and a reduced sta delivery off tothe luting segment) ‘Any salt-osing state ~ spot Uyg >20 molt if eral and <10 mmol if extrarenal Diuretics ~ spot Uys may or may nat* be >20 mmol ‘Advanced chronic renal allure ~a very low GER (-5 mln), less Nis fitted and excreted (though fractional Nav excretion is high) and stl fue deivery is low and may be <3 Vay, hich isthe maximum (Gotenta) volume ofsolutesee water that can be genetated and excreted Acute renal allure ~ no GFR, so ro water excretion. Remember salt intake may continue, because ofthis) Drugs ~ direct stimulation of AVP release or that enhance its action, eg. PGE, enagorism by norsteraidals sans) Endocrine Psychotic polydipsa (-7% of psychic patients) ~ 2 mix of abnor Increased renal sersitvty to AVP, Hypothyroidism ~AVP-dependent (cardiac outpu) and independent (anknovs) mechanisms ‘Glucocorticoid lack (ptltary disease - raised AVP (catdac output and linked to feorteotophin releasing facto), and reduced distal ud delvery (FR) SDM ~ a diagnosis of exclusion (SIADH, sb Table 4 anc Figure 6) Reduced (without edema) Increased (with oedema) Normal (or sig increased, without eedera) thst, AVP dysregulation and ‘Postuetic Na anton. ‘eine soden concentration; GF, loner lation ate; AV, vsopeiin, SDH, andro of nepeapte antic hormone secrton Table 2 the kidneys have the capacity to excrete up to 30 lites of dilute (osmolality <100 mOsm/kg) urine a day, which is sometimes seen in patients with diabetes insipidus (eee Figure 1). Thus, when renal function is normal, 10 Induce hyponatraemia, 30 ltres/day must be drunk; this occurs only in rare cases of primary polydipsia® Therefore, to develop hyponatraemia the kidneys must be unable to generate and excrete enough solute- free water to balance intake. For this to happen there has to bbe too much (or inappropriate) vasopressin secretion or reduced fluid delivery to the ‘diluting segment’ of the TAL (Figure 1), or both. With these underlying abnormalities in mind, a classifica tion of hyponatraemia is set out in Figure 4 and Table 3. Body fuid compartments and osmolality When exposed to hypotonic environment, cells swell and ean initially recover their volume by losing K* and CI”, but in the longer term they will alter (decrease in this instance) production of endogenous solutes used to balance extracelu- Jar osmolality and so stabilize their volume. This is particularly, Important in the brain, a8 itis in a rigid cranium and eannot ‘swell by more than ~10% in response to acute hyponatraemia, ‘The braln Is also more prone to cell shrinkage during rapid correction of chronic hyponatraemia, because of the adaptive loss of intracellular solutes that has occurred. Thus, In treating, hyponatraemia 2 distinction must be made between acute and chronic hyponatraemia ody uid compartments “Total body Fuld = 60% body wet ‘Twosthids isin the ntacelilr space x’ ich (120 mmole) ‘One-third isin the extracellular spaca- Na leh (140 mmole) ‘One quarter of exraceliular Fu is in the nravascular space Ina70kg man Total body Auld = 42 tes Inracliutar uid = 28 tees Extraceluarfulé = 14 Ures InovaseulaeRuid= 3.5 res 4 There is movement of mater between these compartments Figure 3 evans an ovale fm Clini com Bar For penn oo Ne cou won prs | Plasma sodium concentration isan indax | | oftotalbody Mid osmolalty | (9 207 En. i Heth Tas eset 20,2016, Cogrign 820 case Al ps sen‘Aclinical approach to hyponatraemia sNarloss Skin iy ai OT SLOT NR concn t “ha aggro “eaten Nei aise PHO Figure & ‘Though somewhat arbitrary, and based largely on clinical experience, acute hyponatraemia is defined as being present for up to 48 hours; it can be rapidly corrected, but this is only nec: essary ifthe patient is neurologically impaired, with confusion ‘A classification of hyponatraemia Pseudohyponatraemla ~2 (are) measurement artefact due to reduced plasma water, because of excess lipids (igycerides) oF abnormal protens (4 lM) ‘yperosmolar(s-osmolr endothe hyponabaenia ‘+ fypersycaemia and other mperneant solies, but nt urea) + ‘srg (4. TURP) rigatonfids (ment soto ghee) + subarehnad haemorthoge ‘Tue (hypo-asmolar) hyponatraemia (see Table 3) ‘+ ECFVL (TBNa") ~ reduced efecive atrial volume (Na loss) + ECPVT TBH") ~ reduced efecive arterial volume (oedema) + EGFVT (TBR) ~ normal effective arterial volume (0 oedema) ~ SIH (see Table 4 and Figure 6, drues, tess, cortisol, Ta TURP ransurtal resection of he posite; EO, exter Mid vol tune SIADH, ridone of reppropteaikuretchomone; Tana al body sodium corer Toble 3 Develo Cina ot Bara Heath NIS Tos Drone 20 LABORATORY INVESTIGATIONS ‘Hagular venous pressure ‘Postural bloog pressure + Presence ofoedema Se ead PO Waar ita Tene aa aE for fits due to significant brain swelling. (Muscle injury from 2 fit can inevease muscle cell osmolytes and cause a misleading normalization’ of plasma [Na*], and a diagnosis of underlying byponatraemia may be missed, for example, after Bestasy into cation.) In contrast, symptoms and signs in chronle hyponatrae- ‘mia (present for more than 48 hours or of unknown duration) are usually more gradual in onset and often non-specific; although Ps can be much lower than in acute hyponatraemia, it must not be rapidly corrected (<12 mmol/l rise per 24 hours) unless the patient is comatose or fitting, because of the risk of causing ‘osmotic demyelination syndrome (central pontine myelinoss, (CPM). Additional risk factors for CPM are: Pyy< 105 mmol/L, alcoholism, malnutrition and chronic liver disease, Treatment of severe and symptomatic hyponatraemia con- sists of hypertonic saline (3%), which can be combined with the administration of a loop diuretic to increase elecrolyte-free ‘water excretion. The use of lithium or demeclocyeline to induce nephrogenic dlabetes insipidus is no longer favoured, because of their slow onset of action and unpredictable response. Even the newer vasopressin antagonists must be used with caution, because ofthe risk of causing an excessive and rapid diuresis, and a sudden rise in Py. In monitoring therapy, a tonicity bal- ‘ance can be a helpful safeguard, as it takes account separately of the volume of fuid (water) and amounts of Na* and K* (main solutes) given intravenously (input), and the urine volume and amounts of Na* and K* excreted (output) so as to estimate any ret changes in balance water volume versus the amount of solute (in mmol) - over fixed periods of time, an 2a aA an a 6, Forpesonlsceniy. Note ss thot prmssion Copyngh C2018. Ev Alas eee.LUsRATORY INVESTIGATIONS The syndrome of Inappropriate antidiuretic hormone secretion (SIADH): causes and diagnosis Causes: Pulmonary diseases + Bactertl pneumonia + Vira pneumonia + Tuberculosis + Aspergilosis + Asthma + Cystic pros. cancers of = Ponereas = Stomech + Ymphome = Prostate + ung Neurogical diseases + Meningitis + Encephaitis Bron abscess Brain tumours + Neonatal hypoxia + Hydrocephalus Delirium tremens + Muliple sclerosis Diagnosis: * Decreased plasma osmolality (<270 mOsm) ‘+ Inappropriately concotrated urine (>100 mOsm) * Increased urinary sodium concentration + Cinial ewolaemia ‘Absence of any endocine, cardiac ver or ena dseese No diuretic use Plasma vasopressin level inappropriately elevated relative to plasma osmolality ‘No signincant correction of plasma [Nae] wth volume ‘expansion, but improvement ater fluid resticion Tables Hypernatraemia Hypernatraemia almost always reflects water loss. Even if the ‘Kidneys cannot excrete urine of low volume (<0.5 lire) and high ‘concentration (>1000 mOsm/kg), and the patient is polyuric (as in central or nephrogenic diabetes insipidus), hypernatrae- mia does not normally occur unless there is an associated lack. of thirst or no ready access to water. Thus, you should sus- pect: (i) a lesion of the central nervous system affecting thirst; (QO a problem with communication or a physical disability; (li a lack of vasopressin, impaired release or action on the kid heys. AS already mentioned, cells shrink in hypernatraemia and they will try to minimize this by producing endogenous osmo- Iytes, which makes rapid correction dangerous because adapted cells wil swell more in a hypotonic environment, especially brain cells. Therefore, water replacement should be slow to lower Phx ‘at no moze than 12 mmol/l/28 hours (the same as the rate of correction of hyponatraemia). The oral route is the safest, but if intravenous fuid is given, its Na* content musi be lower than that of any ongoing urinary losses (see tonicity balance above). Giving a 5% glucose solution is limited by the rate of glucose ‘metabolism and should not usually exceed 0.3 I/hour. Hypo- and hyperkalaemia In contrast to Na*, most body K° is inside cells (Figure 3): tis the steep gradient from inside to outside that determines the cell membrane resting potential difference (~~70 mV inside), whieh is especially important in excitable tissues like nerve and muscle. Only ~65 mmol K Is present in the ECF, an amount that can be ‘exceeded easily bya dietary intake ranging trom 50 to 100 mmol/ day (a steak meal may contain ~30 mmol K* and should almost double plasma [K*]}. Thus, defending against acute hyperkalae- ‘ia, and is effect on (cardiac) cell membrane potential, is essen- tials it is achieved by moving K* rapidly ino cells by activating the sodium pump, whichis stimulated by insulin and Pr-receptor sympathetle activation (ay-receptor activation has the opposite effect). Longer-term adjustments of K* balance are achieved by the kidneys: urinary excretion of K* is dependent on aldosterone activity and Na* delivery tothe collecting duct.” Hypokalaemia Hypokalaemia is often defined as Py <3.5 mmol/, but this level rately causes problems: patients are not typically symptomatic ‘until Py <2.5 mmol/l or when it has fallen rapidly; significant ‘muscle weakness tends to occur at Py <2 mmol/L True hypo: kalaemia may be due to K* shifts into cells. or from renal for gastrointestinal losses. Dietary deficiency is not usually a cause, unless there is another source of ongoing K* loss. Examples of cell sifte causing hypokalaemia are rapid cell growth (e.g. anabolism following vitamin By; treatment of megaloblastic anaemia), hypokalaemic periodic paralysis (due to a muscle Cai* channel defect), thyrotoxicosis (especially in Asian males) and excessive use of B;-receptor agonists in asthma, ‘To distinguish between extrarenal and renal losses of K* urinary excretion of K* is an important measurement to make (see Figure 5): In hypokalaemia urinary K* excretion should be less than intake; a value of <20 mmol/day (urine/plasme ratio <1.5) Is appropriate and suggests gastrointestinal losses (though not from vomiting, which leads to renal losses). Renal K- loss can be due to increased aldosterone stimulation or 10 yreased Na* delivery, or both (see Table §); it may also be intermittent, as with postauretic Na* retention. Treatment depends on the duration of hypokalaemia: chronic hypokalaemia means" defcitof at east 100 mmol and this should be replaced orally, bt if intravenous replacement is necessary, no more than 20 mmol/hour should be given (preferably through a central venous line). If hypokalaemia co-exists with metabolic acidosis, treat the hypokalaemia frst or it may get worse intially when you correct the acidosis. Hyperkalaeria Causes of hyperkalaemia are listed in Table 6 and are more fr less the opposite of hypokalaemia. In an intensive care setting, think of cell shifts and acute renal failure; in an out- patient setting think of 2 primary lack of aldosterone or a © mor tee! We ets see Dovnlsded fo Cink. com a Sans Hel NHS Tus December 20206, Fer pea te on No oi ses wi prison: Copia G26 Eve be ALS senLABORATORY INVESTIGATIONS Assessment of hypokalaemia Figure 5 Causes of hypokalaemia ‘The Syndrome of Inappropriate Antidiuretic ‘A primary increase in mineralocartcold actly Hormone Secretion (SIADH) Primary byperennisa~ renin and olsterane¥ (not corrected by kw saline): malignant hypertension (-50%) tonal artery stenosis (15%) -tenin-secreting tumour ‘Primery hyperaldesteronism ~ renin “Cons syndrome bilateral adrenal hyperplasia slucocoricoid suppressible hyperaldosteronism rimery increase in @ nonaldesterene mineralocontcld ~ renin ‘and aldosterone &: “Cushing's syndrome -congeital adrenal hyperplasia parent minerlocotcai excess ‘A primary Increase in dlstalNa* delivery (to the collecting duct) jrtis that act upstream ofthe collecting duct -non-eabsorbed anions (eg. bicarbonate or ketoacids) “Met deficiency ‘ADM, antidiuretic hormone; TBF, total body uid: CF, itraceluar Barter’ syndrome ‘uid; ECF, extracluar Mud ldo, aldosterone; ANF, etal -Gitelmats syndrome natures factor SS, sympathetic nervous system; -5 mmol/l, as in hypokalaemia, it is the rate of change in Py (and, from what baseline) that matters more than its absolute value (except when it is >7 mmol/l, even in patients with chronic renal fallure). Acute treatment consists of intravenous calcium chloride (to stabilize the cardiac membrane potential), sodium bicarbonate, glucose plus insulin and/or a f agonist (intrave- ‘ous of inhaled). Chronic treatment includes fludrocortisone, ‘especially if aldosterone levels are low, but watch out for hyper. tension or significant salt and water retention (weight gain); iureties (particularly if there is hypertension) and calcium resonium by mouth or as an enema. In patients with chronic renal failure, remember that fasting (and therefore low insulin levels) can worsen hyperkalaemia, [Metabolic acidosis and alkalosis Metabolic acidosis is defined by a high plasma 11* concentra- tion (low pH <7.4) and low plasma [HCO;) (<25 mmol/L). (The term acidaemia is more correct in describing the state of a low blood pH and the term acidosis in referring tothe processes caus- ing it.) Metabolic acidosis can also be detected as an increase in plasma anion gap (AG), but without a change in pH or plasma [HCO;). AG=P._{P.+Pj-) = ~12 mmol/L with a normal albu- ‘min; some authorities include Py, making the AG higher, but its ‘normal’ value depends on local biochemical measurements and should be checked fist with each laboratory. A reduced albumin (which is negatively charged) will decrease the AG, as will the presence ofa positively charged myeloma protein.” Compensation in metabolic acidosis occurs by the lungs low ting pCO, through hyperventilation and by the kidneys increas- ing NHy synthesis (and thereby generating ‘new’ HCO;) and urinary NH,* excretion, An index of NH,* excretion is the urine ret negative charge of AG: (Ucr[Uha + Ugl), whieh is normally ~80 mmol/L. Causes of metabolic acidosis with an increased AG include ‘labetic ketoacidosis, lactic acidosis, some poisons (ethylene slycol, methanol and asprin), chronic renal failure and (carey) IgA myeloma, Metabolic acidosis with a normal AG and raised plasma CI” concentration (‘hyperchloraemic, acidosis’) can ‘mean a primary loss of HCO; or a failure to excrete H* and/or generate ‘new’ HCO; from NH synthesis and NHy* excretion. ‘The main causes are: gastrointestinal loss of HCO; , as in diar- thoea or small bowel fistula; renal loss of HCO , a8 In proximal renal tubular acidosis (RTA), which is usually part of a renal Fanconi syndrome; impaired secretion of H* by the collecting duct, and reduced NH,* excretion, 35 in distal RTA (with hypo: or hyperkalaemia). ‘Treatment of metabolic acidosis is of is underlying cause, and by giving sodium bicarbonate fit is severe, as well as potassium in situations where it has been lost, such asin diarrhoea, diabetic Ketoacidosis or proximal RTA. Bicarbonate supplementation cannot be used to restore plasma HCO; to normal in proximal RTA, In distal RTA, as in renal failure, it is given mainly to prevent bone loss.©| Metabolic alkalosis is defined as a plasma (1tc0;) >25 mmol/L and a plasma pit > 7.4. Its usually a response to defi- cits in sodium chloride (ECFV depletion) and/or potassium (sec- ‘ondary or primary aldosterone excess). Causes include te effects ‘of diuretics or renal tubular disorders resembling chronic diuretic, use, like Bartter’s and Gitelman’s syndromes, all of which produce losses of Na‘, Cl", K* and Mg?*, or mainly K* loss ‘due to high levels of circulating aldosterone or other mineralocor- ticoid. Eating disorders (bulimia and anorexia nervosa) can also cause striking and episodic alkalosis (with hypokalaemia and bypomagnesaemia) related to bouts of self induced vomiting. ovale rm Ciesey coat ars ath Nis Tru Desens 20,2016, Forplay No oe ues loot person, Copygh C206 hci ne All ngs reveLasorATORYNvESTIGATIONS Unlike in metabolic acidosis, respiratory compensation in meta- bolic alkalosis is small; the Kidneys respond by excreting less Na* and CI", and because of aldasterone’s action (primary or secondary), more K*. Treatment ist replace the deficits in Na*, (l~ and K* and/or to deal with the underlying cause, including {nereased mineraloconicoid activity!" ° REFERENCES 1 Shiey DG, Unwin 8, The stucture and function af tubules. In: Davison AM, Cameron S], Grunfeld, eta, eds. The Oxford textbook of cinial nephrology, 31d ed. Oxford: Oxford University Press, 2005. Shiney DS, Capasso , Salley N, Unwin Rl. 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