Disorders of Sodium and Potassium Metabolism

Physiology:
Regulation of sodium and potassium balance is a complex process, predominantly occurring in the kidney, and involving a number of hormones and other mediators including the renin-angiotensin-aldosterone system. In addition, it is linked to free water balance and overall acid-base status. Renin ! protease produced by the "uxtaglomerular cells of the kidney in response to low renal perfusion pressure, with a minor stimulatory effect from increased sympathetic tone #from epinephrine and norepinephrine$. !ngiotensin II !n octapeptide produced from angiontensin I in the lungs and kidneys. !ctions: %. &timulates cells in the 'ona glomerulosa of the adrenal cortex to produce aldosterone. (. !cts directly on the arterioles to cause vasoconstriction. ). &timulates *a+,-+ exchange in the renal proximal tubule, which also aids in the reabsorption of -./)-. !ldosterone ! steroid hormone that acts in the late distal tubule and collecting duct. !ctions: %. &timulates the reabsorption of *a.l and the secretion of potassium by the principal cells. (. Increases the activity of the -+ !0Pase secretory pumps in the intercalated cells.

!1- #antidiuretic hormone, aka arginine vasopressin$ ! polypeptide synthesi'ed in the hypothalamus and stored in the posterior pituitary, where they are released in response to plasma hyperosmolality and decreased effective circulating volume. 0here is no significant change in !1- levels in mild volume depletion, but in severe volume depletion and hypotension !1levels can far exceed those induced by hyperosmolality. !ctions: %. Increases collecting tubule water permeability by inducing the activation of preformed water channels, leading to a concentration of the urine. #2ediated by !1- 3( receptors$ (. 2ildly increases vascular resistance #2ediated by !1- 3% receptors$ !*P #atrial natriuretic peptide$ ! polypeptide secreted by myocardial cells in the atria #right4left$ in response to atrial stretch, as is seen in hypervolemia. !lthough it has a large number of actions, physiologically it acts as only a weak natriuretic agent. !ctions: %. 5locks sodium reabsorption in the medullary collecting tubules. (. !cts as a direct vasodilator, decreasing systemic blood pressure. ). Increases 67R, possibly through the combination of afferent arteriolar dilation and efferent arteriolar constriction. 8. Inhibits the renin-anigotensin-aldosterone system at a variety of points. 5*P #brain natriuertic peptide$ ! polypeptide secreted by the brain and by myocardium #ventricles4atria$ in response to cardiac failure. Its actions are similar to those of !*P.

Plasma Osmolality vs. Tonicity 0he plasma osmolality #Posm$ is determined solely by the ratio of overall plasma solutes and plasma water. Plasma tonicity is determined by only those solutes that determine the transcellular movement of water. 7or example, since urea is an ineffective osmole, urea accumulation in renal failure does not lead to movement of water across the cell membrane. 1espite their name, osmoreceptors #such as those responsible for !1- secretion$ actually sense plasma tonicity. Hypovolemia vs. Dehydration 1ehydration refers to pure water loss and an intracellular water deficit due to the osmotic movement of water from the cells into the extracellular fluid. -ypovolemia refers to the combination of salt and water loss #as seen in vomiting, diarrhea, bleeding, etc9$. 1ehydrated patients are always hypernatremic, whereas hypovolemic patients are typically normonatremic or hyponatremic. !s hypovolemia comes predominantly at the expense of the extracellular fluid, whereas dehydration comes at the expense of total body water, for dehydration to produce the same degree of extracellular volume depletion as salt and water loss, about (.: times as much fluid would have to be lost. Overview of Regulation of Renal Sodium alance Renal *a+ excretion varies directly with the effective circulating volume #;.3$. In general, it is changes in tubular reabsorption #rather than changes in 67R$ that constitute the main adaptive response to changes in ;.3. !lthough the loop of -enle and distal tubule are important overall segments in *a+ reabsorption, reabsorption here is largely flow dependent. 0he more significant neurohumoral regulation of sodium balance occurs in the proximal and collecting tubules. 1espite the probable importance of aldosterone in sodium excretion, abnormalities in its secretion rarely are associated with derangements in sodium balance because other factors are able to compensate.

/verview of the handling of electrolytes by the nephron:

Hyponatremia
&ymptoms: &ymptoms from a derangement of sodium are not "ust related to the severity of the derangement, but also to the speed of its development. 0hey are generally neurologic in nature, and include headaches, nausea,vomiting, mental status changes, sei'ures, and coma. In hyponatremia, the exact mechanism leading to these symptoms is thought to be cerebral edema created by the osmolal gradient which favors water movement into cells during states of hypotonicity. 0he degree of cerebral edema is much less when the onset of hyponatremia is gradual #4) days$, partially due to the transport of organic solutes #known as osmolytes$ out of neurons and into the extracellular space, minimi'ing fluid shift into the cells. 7or unclear reasons, premenopausal women are less able to undertake this adaptive response.

&igns , ;.6 !bnormalities: 0here are no specific signs or ;.6 changes seen in hyponatremia.

;tiologies:
Primary &odium <oss Poor Intake of &odium ;xcessive beer consumption #known as beer drinker=s potomania$ >0ea and toast diet? #a condition, most often described in malnourished elderly, in which a patient manages to drink ade@uate fluids, despite an otherwise poor diet$. Increased Arinary ;xcretion #&ee sections on hypokalemia and hyperkalemia for more information on these conditions, as most have a greater effect on potassium balance$ 1ecreased sodium uptake in the proximal tubule Proximal #type ($ R0! .arbonic anhydrase inhibitors #e.g. aceta'olamide$ 1ecreased sodium uptake in the thick ascending limb of the loop of -enle <oop diuretics #e.g. furosemide$ 5artter=s syndrome 1ecreased sodium uptake in the early distal tubule 0hia'ide diuretics #e.g. hydrochlorothia'ide$ 6itelman=s syndrome 1ecreased sodium uptake in the late distal tubule !ldosterone deficiency !ldosterone resistance 7luid loss followed by repletion with hyponatremic solutions #for example, excessive sweating in marathon runners, followed by repletion with free water$ Primary Bater ;xcess ;xcessive intake #aka primary polydipsia. ! daily -(/ consumption 4 %:< is needed to develop hyponatremia$ Psychosis ;cstasy -ypothalamic lesions #such as those that occur due to infiltrative disease like sarcoidosis$ 1ecreased water excretion 1ecreased 67R #6enerally seen only with advanced renal failure, as opposed to early renal failure$ Increased !11ecreased effective circulating volume 0rue volume depletion 3omiting 1iarrhea 5lood loss Increased insensible losses !pparent volume depletion #with subse@uent development of hypervolemia$ -eart failure .irrhosis *ephrotic syndrome

Reset osmostat #condition in which !1- levels are appropriately suppressed by hypotonicity, but at a lower plasma osmolality than normal. 0his occurs predominantly in states of severe debilitation, such as malnutrition, metastatic cancer, and advanced tuberculosis. Reset osmostat is occasionally considered a form of &I!1-$ &I!12alignancy &mall cell carcinoma of the lung /ther lung cancers Pancreatic cancer /lfactory neuroblastoma .*& pathology #nearly any type of .*& pathology has been associated with &I!1-$ Pulmonary pathology Pneumonia !sthma,./P1 Pneumothorax 1rugs .arbama'epine I3 .yclophosphamide -aloperidol &&RIs #e.g. fluoxetine, sertraline$ 3incristine,vinblastin,cisplatin !mitriptyline ;cstasy ;xogenous hormones 3asopressin /xytocin 1esmopressin #aka 11!3P$ ;ndocrinopathies -ypothyroidism #unclear mechanism$ !drenal insufficiency #due to cortisol deficiency$ &evere pain of any etiology #most typically following surgery$ 0ranssphenoidal pituitary surgery #due to direct in"ury to the posterior pituitary$ #It has been observed that acutely psychotic patients occasionally suffer from &I!1-. Bhether this is because the psychosis directly leads to !1- release, or because the psychosis and &I!1- are both manifestations of another undiagnosed primary abnormality is unclear.$ .erebral salt-wasting #! rare syndrome has been described in patients with cerebral disease, particularly subarachnoid hemorrhage, that mimics &I!1-$. 0ranscellular shift of water #secondary to hyperosmolality of the plasma$ -yperglycemia #for each %CCmg,d< rise in glucose above %CCmg,d<, D*a+E should fall by %.Fm;@,<$ !dministration of mannitol Pseudohyponatremia #a collection of disorders in which marked elevations of substances result in a reduction in the fraction of plasma that is water and an artificially low sodium concentration$ &evere hyperlipidemia -yperproteinemia

1iagnosis: In diagnosing the etiology of hyponatremia, there are 8 ma"or parameters that should be evaluated status, plasma osmolality #Posm$, urine osmolality #Aosm$, and A*a. overall volume

Patients with reset osmostat can be distinguished from those with &I!1- by their ability to appropriately dilute their urine after an acute oral water load #(Cml,kg$. In reset osmostat, the A osm should drop below %CC m/sm,kg and 4GCH of this water should be excreted over the course of 8 hours. In &I!1-, the A osm will still be 4%CC m/sm,kg, and less than FCH of the water load will be excreted at 8 hours. 1irect measurement of plasma vasopressin levels is not helpful in making a diagnosis of &I!1- because an elevation in his hormone can be seen in all causes of hypotonic hyponatremia #with the exception of primary polydipsia$.

0reatment: Indications for hospitali'ation, aside from those for the underlying disorder, are neurologic symptoms or serum D*a +E I %(: m;@,<. 0he rate of correction should not exceed C.: m;@,<,hr, unless patient is having severe neurologic symptoms, due to the risk of precipitating central pontine myelinosis #aka osmotic demyelination syndrome$. 0his commonly fatal disorder consists of demyelination of loss of axons, predominantly in the pons, as the name implies. It manifests as spastic @uadriplegia, pseudobulbar palsy, and varying degrees of encephalopathy or comaJ in its complete form, patients develop the >locked-in syndrome?. It usually develops 8G-K( hours after correction of hyponatremia. In addition to confusion and spastic @uadriplegia, hori'ontal ga'e paralysis is a clue to the diagnosis. Prognosis is poor, and the diagnosis itself is fre@uently made after death. !lthough most fre@uently associated with rapid correction of hyponatremia, it is also seen in hypernatremia, a'otemia, and hyperglycemia, and is more common in alcoholics. In patients who survive, full recovery may take months.

Hypervolemic hyponatremia

&odium restriction #%-)gm,day$ and free water restriction #%-%.: <,day$

!uvolemic hyponatremia

7ree water restriction only

Hypovolemic hyponatremia

Replace water with C.LH *a.l #normal saline$ measured D*a +E$ x #C.G: in women$

0otal body sodium deficit M C.F x I5B x #%8C

0otal N of < of *& needed to correct D*a+E M *a+ deficit , %:8 m;@,< 1uration of correction #hrs$ M #%8C measured D*a +E$ , C.: m;@,<,hr

Rate of correction #<,hr$ O DI5B #in kg$ , :CC E x C.G: in women

&evere hyponatremia accompanied by sei'ures or coma can be treated more rapidly with )H *a.l.

Hypernatremia
&ymptoms: In hypernatremia, the rise in plasma sodium leads to water movement out of the brain, in which the decrease in brain volume can lead to rupture of the cerebral veins with focal subarachnoid and intracerebral hemorrhage. &ymptoms are generally similar to those which occur in hyponatremia. &evere symptoms usually re@uire an acute rise in serum sodium to above %:Gme@,<.

&igns , ;.6 !bnormalities: 0here are no specific signs or ;.6 changes seen in hyponatremia.

;tiologies:
;xcess intake of sodium #usually rapidly corrects in the setting of normal renal function$ -ypertonic saline solutions #e.g. )H *a.l, *a-./)$ !ccidental or nonaccidental salt poisoning in infants and young children Increased renal reabsorption of sodium #rare cause of hypernatremia because the thirst mechanism which will generally act to normali'e plasma sodium at the expense of mild hypervolemia$ -yperaldosteronism 1ecreased water intake,Increased water excretion #these two categories should be considered together, as any condition which results in increased water loss will only result in hypernatremia if there is concomitant impairment in either thirst or in access to free water, as serum hypertonicity is a very strong promoter of thirst$. Impaired access to water Infants ;lderly patients with dementia or who are bed-bound. Impaired thirst sensation #aka hypodipsia. !lmost always due to hypothalamic disease.$ 0umor 6ranulomatous disease #e.g. sarcoidosis$ 3ascular disease Reset osmostat #aka essential hypernatremia seen only in patients with primary mineralocorticoid excess$ Increased insensible losses 7ever ;xposure to high temperatures ;xercise 6I losses #particularly in osmotic diarrheas$

Impaired reabsoprtion of water in the collecting duct #aka 1iabetes Insipidus or 1I$ !1- 1eficiency #.entral 1I$ 1ecreased Production and,or Impaired Release 7amilial .1I #rare autosomal dominant disorder$ Idiopathic #may be due to an autoimmune process in some patients and occult pituitary or sellar process in others. )C-:CH of cases of central 1I are initially labeled idiopathic$. *eurosurgery #seen most commonly in transsphenoidal surgery and seen in %C-(CH of cases involving the removal of small pituitary adenomas$. 0rauma 0umors ;ncephalitis &heehan=s syndrome #postpartum pituitary infarction$ Infiltrative diseases <angerhans cell histiocytosis &arcoidosis Begener=s granulomatosis -ypoxic encephalopathy Increased 1egradation 6estational 1I #occurs during the second half of pregnancy due to the placenta secreting a vasopressinase, which leads to the rapid degradation of !1-$ !1- Resistance #*ephrogenic 1I due to resistance either at the !1- site of action in the collecting tubules, or due to interference with the countercurrent mechanism, which can be develop from medullary in"ury or from decreased sodium chloride reabsorption in the thick ascending limb of the loop of -enle.$ <ithium toxicity #occurs in up to (CH of patients on chronic lithium therapy, with an additional )CH having subclinical impairment in concentrating ability$. -ereditary *1I #! usually P-linked disorder$. -ypercalcemia #can be seen if serum D.a+(E 4 %% mg,d< consistently$. -ypokalemia #can be seen in serum DQ+E I ) me@,< consistently.$ *eurosurgery #seen in patients after transfrontal surgery for craniopharyngioma$. &ickle .ell 1isease !myloidosis #probably due to amyloid deposits in the collecting tubules$ &"ogren=s disease #probably due to lymphocytic infiltration around the collecting tubules$ 1ecreased 67R from any cause #partial nephrogenic 1I is a relatively common finding in hospitali'ed and elderly patients due to decreased 67R, however, the mild to moderate decline in urine concentrating ability is not usually sufficient to produce polyuria and,or hypernatremia, though may play a contributing role when another etiology of hypernatremia is also present.$ Primary Impairment in the counter-current mechanism /smotic diuresis #from mannitol, glucose, or urea$ Internal redistribution of water #occurs due to hyperacute increase in intracellular osmolality, most often from the rapid breakdown of glycogen into lactate. 0he hypernatremia usually resolves within :-%: minutes from cessation of activity$ 3igorous exercise &ei'ures

1iagnosis:

!s noted elsewhere, all causes of hypernatremia must also be in the setting of either impaired access to free water or an impaired thirst mechanism due to hypothalamic disease, as plasma hyperosmolality is a powerful inducer of thirst. 0reatment: 0he rate of correction should not exceed C.: m;@,<,hr, unless patient is having severe neurologic symptoms, due to the risk of precipitating cerebral edema, sei'ures, and death. 7ree Bater 1eficit M 0otal 5ody Bater x D#Plasma D*a +E , %8C$ %E 0otal 5ody Bater #<$ M C.F x I5B #kg$ x #C.G: in women$ x #C.L if patient appears hypovolemic$ 1uration of correction #hrs$ M D#Plasma D*a+E$ %8CE , C.: Rate of .orrection #<,hr$ M #7ree Bater 1eficit$,#1uration of .orrection$ % #*a.l content of replacement fluid , C.LH$ Asing substitution, the rate of correction #m<,hr$ M (.% x I5B x #C.G: in women$ x #C.L in hypovolemia$ % #*a.l content of replacement fluid , C.LH$ #*ote that only the duration of correction, and not the rate, is dependent upon the initial D*a +E$ If patient is hypovolemic, one should use R *& or S *&. If patient is hypervolemic, one should give 1:B + I3 furosemide It is important to note, that while the patient is receiving corrective I3 fluid replacement, he is continuing to experience free water loss #which also needs to be replaced$ unless the initial etiologic cause has been identified and appropriately treated #such as treatment for an osmotic diarrhea$.

Hypo"alemia
&ymptoms: *ausea,vomiting, weakness, muscle cramps &ymptoms generally do not occur unless plasma DQ+E I ).C, except in heart disease and cirrhosis, in which case symptoms can occur with more mild abnormalities. ;.6 !bnormalities: 2ild #).C-).: m;@,<$ 2oderate #(.:-).C m;@,<$ 0 waves lose amplitude 0 waves become flattened, &0 segments become depressed, and A waves become more prominent. !rrhythmias may develop especially if the patient is taking digitalis. Risk of arrhythmias rises @uickly. TR& prolongation may also occur but is uncommon.

&evere #I(.: m;@,<$

.ontrary to popular belief, the T0 interval does not prolong in hypokalemia. 0his appearance is the result of the prominent A wave and 0A fusion. ;tiologies:
Poor intake #Ancommon in isolation, but can often worsen hypokalemia due to another cause$ !norexia nervosa , 5ulimia >0ea and toast? diet 1ecreased 6I !bsorption 1iarrhea 3illous adenoma #rare$ Areterosigmoidostomy #probably due to urine ammonium ions competing with potassium for absorption$ <axative abuse 3omiting , *6 drainage #hypokalemia in these settings are largely due to metabolic alkalosis leading to excessive sodium bicarbonate delivery to the distal tube, in addition to hypovolemia inducing aldosterone release$. Increased Arinary ;xcretion 1ecreased reabsorption in the loop of -enle 2edications <oop diuretics #e.g. furosemide$ 5artter=s syndrome #a rare autosomal recessive disorder which grossly mimics treatment with a loop diuretic$. Increased excretion in late distal tubule Increased delivery of sodium to the distal tubule Proximal #type ($ R0! 7anconi=s syndrome !myloidosis 2ultiple myeloma 0hia'ide diuretics #e.g. hydrochlorothia'ide$ <oop diuretics #e.g. furosemide$ 6itelman=s syndrome #an uncommon autosomal recessive disorder caused by a defect in the *a-.l cotransporter in the early distal tubule. 0his, combined with the more serious 5arrter=s syndrome, are rare etiologies of hypokalemia and metabolic alkalosis in a normotensive patient. 0ogether, these are often referred to as salt-wasting nephropathies$ .arbonic anhydrase inhibitors #e.g. aceta'olamide. 2imics proximal R0!$ 1Q! #due to glucose osmotic diuresis. 0rue potassium depletion is usually masked by transcelluar shifts until correction of the acidosis$

Reduced function of Q+,-+ !0Pase in the late distal tubule 0he most common form of distal #type %$ R0! !utoimmune #best described in &"ogren=s syndrome$ 3ariety of hereditary defects Increased permeability of the luminal membrane to potassium !mphotericin 5 ;xcess mineralocorticoids ;levated serum aldosterone Primary hyperaldosteronism !ldosterone-secreting adrenal adenoma #F:H of cases of %U hyperaldosteronism$ Idiopathic adrenal hyperplasia .ongenital adrenal hyperplasia %KV hydroxylase deficiency %%W hydroxylase deficiency !drenal carcinoma 7amilial hyperaldosteronism &econdary hyperaldosteronism Renovascular hypertension Renal artery stenosis Renal artery atherosclerosis Renal artery vasculitis Renin secreting tumor Pseudohyperaldosteronism .ushing=s syndrome #due to the mineralocorticoid actions of the excessive cortisol$ ;xogenous mineralocorticoids 7ludrocortisone acetate #aka 7lorinef$ Intranasal corticosteroids ;xogenous %%W hydroxysteroid dehydrogenase inhibitors 6lycyrrhi'ic acid #present in licorice and some chewing tobacco$ Increased delivery of non-reabsorbable anions to the distal nephron #in this setting, more of the sodium delivered to the late distal tubule will be exchanged for potassium$ 3omiting,0ype ( R0! #due to bicarbonate$ 1Q! #due to W hydroxybutyrate$ &evere chronic polyuria #due to excessive filtration of potassium overwhelming the reabsorption capacity of the nephron. 0his is seen most predominantly in psychogenic polydipsia.$ 0ranscutaneous losses from copious perspiration Internal Redistribution !lkalosis #a relatively small effect, with a decrease in plasma DQ+E of C.8me@,< for every C.% unit rise in p-$ Increased availability of insulin #seen most commonly during treatment for 1Q! or non-ketotic hyperglycemia coma$ -igh catecholamine states #predominantly seen in severe acute illness, and coronary ischemia$ -ypokalemic periodic paralysis #a rare disorder of uncertain cause characteri'ed by potentially fatal episodes of muscle weakness or paralysis which can affect the respiratory muscles$ 2arked increase in blood cell production 1uring treatment for megaloblastic anemia with folic acid or vitamin 5%( 1uring treatment for neutropenia with 62-.&7 !cute myeloid leukemia Anknown 2echanism -ypomagnesemia

1iagnosis:

!ll patients with hypokalemia and hypertension should be screened with plasma aldosterone and renin levels for signs of primary or secondary hyperaldosteronism. !n elevated plasma aldosterone to renin ratio is suggestive of primary hyperaldosteronism, which should be confirmed by an aldosterone suppression test.

0reatment: !s there is no strict correlation between plasma potassium concentration and total body potassium stores. In general, for every %m;@,< that the plasma potassium is below 8.C, there is a total body deficit of (CC-8CCme@. Repletion of potassium should always be accompanied by repletion of magnesium in hypomagnesemic states. 2ild to moderate hypokalemia #DQ+E 4 ).C$: 0reat the underlying disorder, if possible X FC-GC m;@,day of P/ Q.l Q-sparing diuretics are more effective in hypokalemia due to chronic diuretic use I3 Q.l #%C-(C m;@,hr. ! maximum of FCm;@ should be given via a single peripheral vein$ &imultaneous supplementation with P/ Q.l

&evere hypokalemia #DQ+E I ).C, or symptomatic$:

Increasing intake of potassium-rich foods as chronic treatment of hypokalemia is less effective than potassium chloride supplementation, due to their generally high content of phosphate and citrate.

Hyper"alemia
&ymptoms: &ymptoms of hyperkalemia can be related to impaired neuromuscular transmission, the most prominent of which is muscle weakness. &evere symptoms usually do not occur until the plasma DQ+E 4 K.C me@,< #unless the rise has been very rapid$. -ypocalcemia and metabolic acidosis can increase the toxicity of excess potassium, and the risk of developing symptoms and cardiac arrhythmias.

;.6 !bnormalities:

2ild to 2oderate #:.:-K.C m;@,<$ 2arked #K.C-L.C m;@,<$

0all, narrow, peaked 0 waves develop. P wave amplitude decreases, TR& widening and &0 changes develop. &inus arrest or varying degrees of !3 block may occur. TR& becomes >sinusoidal? in appearanceJ cardiac arrest #usually from ventricular fibrillation$ @uickly follows.

&evere #4L.C m;@,<$

In marked and severe hyperkalemia, the atrial muscle may be paraly'ed, with normal ventricular contraction. !s the normal sinus impulses conducting to the !3 "unction without activating the atria, this situation may mimic a "unctional rhythm.

;tiologies:
Increased 1ietary Intake #does not lead to hyperkalemia unless very acute ingestion of 48CCme@ Q.l over % day, or in the setting of other causes of hyperkalemia, such as renal failure$ Increased 6I absorption Aretero"e"unostomy 1ecreased Arinary ;xcretion #which is due solely to decreased excretion in the late distal tubule$ 1ecreased number of functioning nephrons Renal failure #does not occurs until 67R I (Cm<,min, and will not occur as an isolated cause of hyperkalemia until 67R I :m<,min$ 1ecreased delivery of sodium to the late distal tubule 1ecreased effective circulating volume #due to stimulation of the conversion of prorenin to renin, leading to increased circulating angiotensin II and increased reabsorption of sodium in the proximal tubule$ -eart failure .irrhosis 0ype ( psuedohypoaldosteronism #aka 6ordon=s syndrome, or familial hyperkalemic hypertension a genetically heterogenous, but phenotypically homogenous, group of rare hereditary disorders associated with increased activity of the *a-.l cotransporter in the early distal tubule$. Impairment of potassium excretion in the late distal tubule !ldosterone deficiency #aka hypoaldosteronism or type 8 R0!$ Primary aldosterone deficiency Primary adrenal insufficiency #aka !ddison=s disease$ .ongenital adrenal hyperplasia (%-hydroxylase deficiency -eparin and <2B- #due to a direct toxic effect on the adrenal 'ona glomerulosa cells$ -yporeninemic hypoaldosteronism 1iabetic nephropathy #due to impaired conversion of prorenin to renin$ !cute glomerular nephritis

*&!I1s #due to the fact that renin secretion is normally mediated in part by locally produced prostaglandins, the production of which is inhibited by *&!I1s. 0his occurs predominantly in patients with renal insufficiency.$ -I3 #unknown mechanism$ Impaired conversion of angiotensin I to angiotensin II !.; inhibitors &evere illness #hypersecretion of !.0- in severe illness may diminish aldosterone production by shunting precursors to the synthesis of cortisol$ !ldosterone resistance #aldosterone levels may be normal or even high$ 5lockage of the normal sodium channel in the principal cell #reabsorption of sodium in the late distal tubule and collecting duct is necessary to make the lumen electronegative, which promotes the movement of both Q+ and -+ into the urine$ Potassium sparing diuretics #e.g. spironolactone, amiloride, triamterene$ 0rimethoprim Pentamidine 0ype % pseudohypoaldosteronism #heterogeneous group of rare hereditary disorders which usually present in infancy$ !utosomal recessive form #due to a defect is in the sodium channel in the collecting tubule and other aldosterone target organs - making it relatively unresponsive to aldosterone$ !utosomal dominant form #due to mutations in the gene for the mineralocorticoid receptor. Patient with this form may clinically improve with age$ &elective impairment of potassium secretion !cute transplant re"ection <upus nephritis !myloidosis &ickle-cell disease /bstructive uropathy .yclosporine #specific mechanism is not entirely clear, but this effect can be particularly pronounced when cyclosporine is combined with an !.; inhibitor$ Internal Redistribution 0ranscellular shift !cidosis #DQ+E increases by C.Fm;@,< per C.% decrease in p-$ 5eta blockers #rare cause of clinically significant hyperkalemia in isolation, but can be a significant factor when combined with another cause of hyperkalemia such as extreme exercise in the setting of W blocker use$ ;xercise #typically associated with mild rebound hypokalemia occurring several minutes after rest$ 1igoxin toxicity Ancontrolled I112 #due to insulin deficiency$ &uccinylcholine -yperkalemic periodic paralysis #an autosomal dominant disorder in which episodes of weakness or paralysis are usually precipitated by cold exposure, rest after exercise, or the ingestion of small amounts of potassium.$ .ell lysis Rhabdomyolysis 0umor lysis syndrome Ischemic bowel. Pseudohyperkalemia .ell lysis during,following phlebotomy #strongly suggested by the reddish tint of the serum due to the concomitant release of hemoglobin$ 2echanical trauma 0emperature-dependent leakage of potassium out of R5.s -ereditary spherocytosis 7amilial pseduohyperkalemia Post-clot transcellular shift #potassium moves out of white blood cells and platelets after clot formation. 0his effect is minimal in patients with normal cell counts, but can be pronounced in extreme leukocytosis or thrombocytosis$

1iagnosis: 7irst, rule out pseudohyperkalemia, cell lysis and transcellular shifts. 0hen proceed with the following algorithm:

0reatment: 1rug .alcium 1osing %Cm< of %CH calcium gluconate, given over (-) minutes with constant cardiac monitoring %C units regular insulin + % amp 1:C, followed by continuous glucose infusion (Cmg in 8m< saline inhaled over %C minutes :C me@ I3, given over : minutes 3aries, but can give 8Cmg I3 (C grams given with %CCm< of a (CH sorbitol solution P/ or PR, @8-Fhrs 2echanism !ntagoni'es membrane actions of Q+ 1rives Q+ into cells 1rives Q+ into cells 1rives Q+ into cells Removes Q+ from the body Removes Q+ from the body Removes Q+ from the body 0ime to /nset I: minutes 1uration of ;ffect )C-FC minutes

Insulin + 6lucose !lbuterol &odium 5icarbonate 7urosemide Qayexalate 1ialysis

%: -)C minutes %:-)C minutes )C minutes )C minutes FC minutes I : minutes

8-F hours % hour ( hours 8-F hours 8-F hours -