- Prof. Dr. Maheshkumar ‘s UnitDr. Israel

History:Present complaints:

complains of weakness of both lower and upper limbs for past 3 days

HOPI:A 40 / M , Sanjivi , apparently healthy individual developed sudden onset weakness of both lower limbs involving both proximal n distal muscle groups 3 days back

6hrs later , pt developed weakness of both upper limbs equally involving proximal and distal muscles

H/o difficulty to stand from bed, getting up from squatting positions

H/o difficulty to turn from side- side in bedH/o buckling of knee jointsH/o difficulty to raise the hand and mixing foodNo H/o any sensory disturbancesNo h/o any bowel bladder disturbancesNo h/o suggestive of any cranial nerve involvementNo h/o fever cough sore throatNo h/o vomiting loose stools No h/o excessive sweating , No h/o oliguria polyuria hematuriaNo h/o seizure headache backpainNo h/o dysnoea palpitatios chest painNo h/o any diuretic intakeNo h/o recent vaccination , dog biteNot a k/c/o HTN DM

o/e:Pt conscious oriented afebrile fairly

hydratedNo icterus cyanosis pallor pedal edema P – 82 /minBP – 100/70 mm hgSingle breath count : upto 26CVS - S1 S2 heard . No murmurRS - NVBS . No added soundsPA – soft nontender. Bowel sounds +nt

CNS:HMF – NADNo meningeal involvementCranial nerves – normalSpino – motor examination:Tone: decreased in all 4 limbsPower : upper limbs 4/5

lower limbs 2/5DTR: bicep + +

triceps + +supinator + +knee + +ankle + +Plantar B/L no response

Sensory – normalCerebellar – normalAutonomic system - normal

Provisional Diagnosis:Quadriparesis

? GBS ? HypokalemicInvestigation:Hb: 12.8 gm %TC : 8200 DC : P55, L37 , M8PCV : 38.2 %MCV : 87.3 flMCH : 27.7 pgRBC : 4.4 millionPlatelet : 2 lac

RBS : 323 mg% BUN:58S. Cr : 1.1Na+ : 138K+: 3.1PVT Reports

Na + : 137K+ : 2.17HCO3- : 23.7Cl- : 93.4

FBS : 109 mg/dlPLBS : 112 mg /dl

ECG

Nephrology Opinion:suggested the following investigations:

ABG analysis24 hrs urine electrolytesUSG abdomenS. K+ levels monitoringS. Ca+ and Mg + levels

ABG analysis :pH : 7.56HCO3 : 30.1 mmol/lPaCO2 :49.0 mm HgPa02 : 80.6 mm HgSaO2 : 96 %Na+ : 138 mmolK+ : 2.69mmolCl - : 96 mmol

INTERPREATION:metabolic alkalosis with respiratory compensation

24 hrs urine report :Volume : 4.43 litProtein : 332 mg /dNa +: 225meq /d ( high )K+ : 22.55 meq / d ( high )Cl- : 320 meq / d ( high )Ca+ : 56 mg /d ( low )Mg+ : 155.5 mg /d ( normal )

SERUM LEVELS :

S. Ca +: 10.6 mg /dl ( high normal )12.2 mg/ dl (GSH central lab report )

S. Mg+ : 1.9 mg/dl ( low normal )

USG :B/L medical renal disease RK : 9.8 x 4.6 cmLK : 10.4 x 5CMD preservedMildly increased cortical echoes in both

kidneysno evidence of calcinosisLIVER , SPLEEN , PANCREAS : normal

Treatment given: IV fluids ( RL )Inj. CefotaximeInj RanitidineInj KCl ( 10 meq/hr for 4 hrs )Syp. KCl T. BCT Diet adviced ( to include coconut water;citrus

juices ) Course In Hospital:

the next day the power in the limbs improved.pt was able to walk.

Nephrology opinion :f/s/o GITELMANN’s Syndrome

Hypokalemia can only occur for four reasons: Decreased intake Shift into cells Extra-renal losses Renal losses

HypokalemiaHypokalemia

Urinary KUrinary K++ excretion excretion

< 15 < 15 mmol/dmmol/d

Assess acid-base statusAssess acid-base status

Metabolic Metabolic acidosisacidosis

MetabolicMetabolicalkalosisalkalosis

LowerLower gastronitestigastronitestinal nal KK++ loss loss

Remote diuretic use Remote diuretic use Remote vomitingRemote vomitingKK++ loss via sweat loss via sweat

> 15 > 15 mmol/dmmol/d

Assess KAssess K++ secretion secretion

TTKG > 4TTKG > 4 TTKG < 2TTKG < 2

Acid-base statusAcid-base status

NaNa++-wasting-wasting nephropathynephropathyOsmotic diureticOsmotic diureticDiureticDiuretic

Metabolic acidosisMetabolic acidosis

Diabetic ketoacidosisDiabetic ketoacidosisProximal (type 2) RTAProximal (type 2) RTADistal (type 1) RTADistal (type 1) RTAAmphotericin BAmphotericin B

Metabolic alkalosisMetabolic alkalosis

Hypertension ?Hypertension ?

YesYes

MineralocortMineralocorticoid excess icoid excess Liddle’s Liddle’s syndromesyndrome

NoNo

VomitingVomitingBartter’s syndromeBartter’s syndromeExclude diuretic abuseExclude diuretic abuseHypomagnesemiaHypomagnesemia

Causes of hypokalemia

Decreased intake: kidney can conserve to 5-25 mEq K+ daily; normal intake 40-120 daily.

Shift into cells: Alkalosis Insulin Beta adrenergic stimuli

Stress Beta agonists- e.g.: albuterol, ritodrine

Increased potassium entry into cells: Hypokalemic periodic paralysis-

typically oriental men with thyrotoxicosis; ? abnormal Ca++ channel; ? Increased Na/K atp ase activity.

Increased rbc uptake, e.g. after treatment with B12, folate.

Extra-renal losses of potassium:

Gastrointestinal losses of potassium Gastric juice contains 5 – 10 mEq

K+/L. Intestinal fluids contain 20 – 50

mEq/L

Hypokalemia from loss of gastric fluid. Loss of hydrogen ion increases plasma

bicarbonate. Coexisting volume depletion increases

aldosterone secretion. Increased delivery of bicarbonate to the

distal nephron obligates a cation. In the setting of increased aldosterone levels, sodium is retained and potassium excreted.

Potassium loss is most prominent early. Actual losses in gastric juice are relatively

small.

Diarrheal losses are usually accompanied by metabolic acidosis Villous adenoma Laxative abuse

Sweat losses- 5 – 10 mEq/L

The kidney and potassium

Nearly all potassium filtered at the glomerulus is reabsorbed in the proximal nephron. Urinary potassium is the result of distal potassium secretion.

To excrete potassium, the kidney requires an adequate number of nephrons, aldosterone, and a circulation adequate to provide adequate distal delivery of sodium for sodium/potassium exchange.

Renal losses of potassium Diuretics- activate the renin-

angiotensin-aldosterone cascade. Primary aldosteronism/increased

steroids. Presentation of a non-resorbable anion

distally, obligating a cation, which will lead to increased potassium excretion in the presence of aldosterone. Bicarbonate Penicillin derivatives Betahydroxybutyrate

Renal losses of potassium

Renal tubular acidosis Proximal, especially with therapy Some distal types Type IV RTA patients are typically

hyperkalemic

• Hypomagnesemia• Polyuria

What data do we want to diagnose the cause of hypokalemia in this pt?

Urinary potassium: 24 hour values better than spot specimens.

Aldosterone and renin levels. Blood pressure measurements. A history.

Therefore:

Potassium is being lost in the urine. Primary aldosteronism is r/o by

normal blood pressures. ABG r/o renal tubular acidosis. Diuretic abuse R/o history

Bartter’s and Gitelman’s syndromes Bartter’s syndrome is usually diagnosed

in childhood, sometimes associated with growth and mental retardation. The defect is impaired NaCl reabsorption in the loop of Henle. Findings are similar to administration of a loop acting diuretic: Salt loss leading to volume depletion and

activation of the renin-angiotensin system Increased urinary calcium

Bartter’s and Gitelman’s Syndromes 3 or 4 types of Bartter’s have been

identified:• Defects in the luminal Na-K-Cl transporter• Defects in the luminal potassium channel• Defects in the basolateral chloride channel

Gitelman’s syndrome

Like Bartter’s an autosomal recessive disorder, but not usually diagnosed early in life.

Findings mimic administration of a thiazide diuretic: the defect is in the Na-Cl transporter.

Patients may complain of polyuria, cramps. They do not have hypercalciuria, but

typically have low serum magnesium levels.

Gitelman’s syndrome

Diagnosis is made by history as well as lab findings. Lab findings are indistinguishable from thiazide use: Hypokalemia, hypomagnesemia,

increased renin and aldosterone levels, decreased urinary calcium.

Genetic screening?

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1: Clin Nephrol. 2001 Mar;55(3):233-7.Related Articles, Links

Mimicry of surreptitious diuretic ingestion and the ability to make a genetic diagnosis.

Schepkens H, Hoeben H, Vanholder R, Lameire N.

Department of Internal Medicine, University Hospital Gent, Belgium. katrien.vanrenterghem@rug.ac.be

Gitelman's syndrome, also known as "hypocalciuric variant of Bartter's syndrome", is a cause of chronic hypokalemia and hypomagnesemia in adults. A specific gene has been found responsible for this disorder, encoding the thiazide-sensitive NaCl coporter (TSC) in the distal convoluted tubule. We describe a psychiatric patient with chronic symptomatic hypokalemia and hypomagnesemia whose electrolyte disturbances were subsequently misdiagnosed as an acute alcohol and benzodiazepine withdrawal syndrome, as chronic diuretic abuse and as a classical Bartter's syndrome. Finally, genetic investigation revealed the presence of mutations in the SLC12A3 gene leading to the proper diagnosis of Gitelman's syndrome. We emphasize that Gitelman's syndrome should be suspected in every hypokalemic patient with biochemical resemblance of diuretic ingestion, especially when repeated toxic screens for diuretics are negative. The ability to make a molecular-genetic diagnosis can be of practical benefit in confusing clinical settings.

                                                           

  

Gitelman’s syndrome: treatment Potassium Magnesium Aldactone or amiloride ACEI’s NSAIDS of no benefit

General comments about the treatment of hypokalemia Think about the cause of the

hypokalemia you are treating? A cellular shift, e.g. hypokalemic periodic paralysis, will require a lot less potassium to correct than hypokalemia from potassium loss.

Orally or i.v.? Orally is safer; limit i.v. repletion to 20 mEq./hour except in very unusual circumstances- then monitor.

Anticipate: has K+ loss stopped or will it be ongoing?

Are you giving other drugs that will influence K+ levels? E.g. NSAIDs, ACEIs, ARBs.

Generally, use KCl vs. other preparations.

Followup with repeat levels- consider using the replacement protocols.