Case of Case of HypokalemiaHypokalemia

Dr.K.VidhyaDr.K.VidhyaUnit VII, Dept of medicineUnit VII, Dept of medicine

Prof.Dr.P.VijayaragavanProf.Dr.P.Vijayaragavan

venkatesh, venkatesh, 41 yr old male 41 yr old male , , Welder by occupationWelder by occupation

……admitted withadmitted with

C/O Weakness of all 4 limbs for the C/O Weakness of all 4 limbs for the past 3 days…past 3 days…

Acute onset, initially felt as Acute onset, initially felt as limbs becoming heavy and then was limbs becoming heavy and then was unable to move his limbs : gets unable to move his limbs : gets severe pain when attempting to use severe pain when attempting to use the muscles the muscles

H/O inability to turn in bed H/O inability to turn in bed from side to side +from side to side +

H/O difficulty in lifting head H/O difficulty in lifting head from pillow +from pillow +

Progressive nature (initially Progressive nature (initially pronounced in lower limb than upper limb)pronounced in lower limb than upper limb)

H/O severe pain in the muscles +H/O severe pain in the muscles +

No H/O Bladder / Bowel involvementNo H/O Bladder / Bowel involvement

No H/O Headache No H/O Headache

H/O vomiting + for 2 days H/O vomiting + for 2 days

No H/O Fever / Passage of loose stools No H/O Fever / Passage of loose stools

No H/O Cranial nerve defects / Sensory No H/O Cranial nerve defects / Sensory deficitsdeficits

No H/O Head trauma / Neck painNo H/O Head trauma / Neck pain

No H/O similar illness in the past.No H/O similar illness in the past.

No H/O admissions in the pastNo H/O admissions in the past

No H/O DM / PT / BA / Seizure No H/O DM / PT / BA / Seizure disorder.disorder.

No H/O any drug intake in the No H/O any drug intake in the past.past.

Family historyFamily history

No H/O similar illness in the No H/O similar illness in the familyfamily

Past HistoryPast History

Personal historyPersonal history

Born out of non consanguineous Born out of non consanguineous marriagemarriage

FTND : Antenatal & postnatal history FTND : Antenatal & postnatal history uneventfuluneventful

He is married : two children +He is married : two children +Non smokerNon smokerConsumes alcohol for the past 15 Consumes alcohol for the past 15

years on & offyears on & off

General ExaminationGeneral Examination

ConsciousConsciousOrientedOrientedAfebrileAfebrileHydration fairHydration fairNo Pallor / Icterus / Cyanosis /Clubbing / No Pallor / Icterus / Cyanosis /Clubbing /

Dyspnoea Dyspnoea No GLA/thyroid swellingNo GLA/thyroid swellingHt : 158 cm Wt : 58 kgHt : 158 cm Wt : 58 kg

PR : 76 / min : Regular : N volume : PR : 76 / min : Regular : N volume : N character : Peripheral pulses N character : Peripheral pulses equally felt equally felt

BP : 124/70 mm hgBP : 124/70 mm hg (Trosseau’s (Trosseau’s sign + )sign + )

RR : 14 / minRR : 14 / min

Systemic ExaminationSystemic Examination

CENTRAL NERVOUS SYSTEMCENTRAL NERVOUS SYSTEM : :

HIGHER FUNCTIONS: NormalHIGHER FUNCTIONS: Normal CRANIAL NERVES: No deficitsCRANIAL NERVES: No deficits

MOTOR SYSTEM:MOTOR SYSTEM:

RIGHTRIGHT LEFTLEFT

BULKBULK NormalNormal NormalNormal

TONETONE HypotonicHypotonic

(pain +)(pain +) HypotonicHypotonic

(pain +)(pain +)

POWER POWER (UL)(UL)

1/51/5 1/51/5

POWER POWER (LL)(LL)

1/51/5 1/51/5

REFLEXESREFLEXES

AnkleAnkle AbsentAbsent Absent Absent

KneeKnee SluggishSluggish

SluggishSluggish

BicepsBiceps AbsentAbsent

AbsentAbsent

TricepsTriceps AbsentAbsent

AbsentAbsent

PlantarPlantar FlexorFlexor FlexorFlexor

AbdominalAbdominal PresentPresent PresentPresent

SENSORY SYSTEM EXM : NormalSENSORY SYSTEM EXM : NormalCEREBELLUM : Not examinedCEREBELLUM : Not examinedSIGNS OF MENINGEAL IRRITATION : SIGNS OF MENINGEAL IRRITATION :

Absent AbsentSPINE & CRANIUM : NormalSPINE & CRANIUM : Normal

OTHER SYSTEMS : WNLOTHER SYSTEMS : WNL

Problems

QuadriplegiaQuadriplegia Muscle crampsMuscle cramps Trousseau’ s sign + veTrousseau’ s sign + ve

DiagnosisDiagnosis

Case of….Probably a Mixed electrolyte Case of….Probably a Mixed electrolyte imbalance…imbalance…

HYPOKALEMIA with HYPOCALCEMIAHYPOKALEMIA with HYPOCALCEMIA

InvestigationInvestigation

CBC : (21/6/10)CBC : (21/6/10)

Hb 12.4 mg/dlHb 12.4 mg/dl

TC 7500 cells/mm^3TC 7500 cells/mm^3

DC P65 L32 E3DC P65 L32 E3

ESR 2/5ESR 2/5

Plt 1.2 lacs/mm^3Plt 1.2 lacs/mm^3

PCV 38%PCV 38%

RBS - 60 mg/dlRBS - 60 mg/dlBlood urea - 26 mg/dlBlood urea - 26 mg/dlSr creatinine - 0.9 mg/dlSr creatinine - 0.9 mg/dlSr. ElectrolytesSr. Electrolytes

Na - 126Na - 126

Cl - 103Cl - 103

K - 2K - 2

HCO3 -24HCO3 -24

Urine :Urine :

alb & sugar – nilalb & sugar – nil

deposits 1-2 pus cells/hpfdeposits 1-2 pus cells/hpf• CXR PA – NADCXR PA – NAD• ECGECG(21/6/2010) – (21/6/2010) – SR / ST SR / ST

sagging /T wave inversion sagging /T wave inversion /prominent U waves in chest /prominent U waves in chest leadsleads

• HIV - NegativeHIV - Negative• Sr calcium Sr calcium (22/6/2010)(22/6/2010) – 4 – 4• LFT : NLFT : N

Treatment givenTreatment given

Correction of K +Correction of K +Correction of Ca ++Correction of Ca ++

… … Proceeded to detect the causeProceeded to detect the cause

ABG ABG

ABGABG 24/6/201024/6/2010 29/6/201029/6/2010

PCO2PCO2 42.15mm hg42.15mm hg 41.82mm hg41.82mm hg

PHPH 7.477.47 7.497.49

K+K+ 1.81mmol/l1.81mmol/l 2.97mmol/l2.97mmol/l

HCO3HCO3 27.18mmol/l27.18mmol/l 26.76mmol/l26.76mmol/l

Metabolic alkalosisMetabolic alkalosis

41 year old male , with no significant 41 year old male , with no significant past history , normotensive admitted past history , normotensive admitted with… with…

HypokalemiaHypokalemiaHypocalcemiaHypocalcemiaMetabolic alkalosis….Metabolic alkalosis….

? Gitelman’s syndrome? Gitelman’s syndrome

Repeated electrolytesRepeated electrolytes

23/623/6 25/625/6 27/627/6 30/630/6

Sr K +Sr K + 2.92.9 3.13.1 2.82.8 3.23.2

Sr Ca +Sr Ca +++

44 6.16.1 6.56.5 88

24 hr urine for24 hr urine for……

K+ - 38.3 meq (25 – 125)K+ - 38.3 meq (25 – 125)Cl- - 268.7 meq (110 – 250)Cl- - 268.7 meq (110 – 250)Ca++ - 542.5 meq (100 – 320)Ca++ - 542.5 meq (100 – 320)

Sr. MagnesiumSr. Magnesium – – 2.5 2.5 mg/dl mg/dl (1.7 – 2.55)(1.7 – 2.55)

Nephrology Nephrology opinion(2/7/10)opinion(2/7/10)

Impression : Impression : Bartter’s syndromeBartter’s syndromeAdvice : X Ray KUBAdvice : X Ray KUB

USG AbdomenUSG Abdomen

To transfer the patient to nephrology To transfer the patient to nephrology ward…ward…

X Ray KUB – no features of X Ray KUB – no features of nephrocalcinosisnephrocalcinosis

USG Abdomen – Normal studyUSG Abdomen – Normal studyRepeat ECG (5/7/2010) - WNLRepeat ECG (5/7/2010) - WNL

Case of …Case of …

• Normal blood pressureNormal blood pressure• HypokalemiaHypokalemiaMetabolic AlkalosisMetabolic AlkalosisU K > 30 meq / dayU K > 30 meq / dayU Cl ^edU Cl ^edU Ca ^edU Ca ^edNormal Mg++ levelsNormal Mg++ levels … … with Hypocalcemiawith Hypocalcemia

HYPOKALEMIAurine potassium >30 mEq/day

Metabolic alkalosis

Urine chloride<20 mEq/liter Urine chloride>20 mEq/liter

•Nasogastric suction•vomiting

Blood pressure

NORMOTENSIVE/ HYPOTENSIVEHYPERTENSIVE

•BARTTER’S SYNDROME•GITELMAN’S SYNDROME•AGGRESSIVE DIURETIC USE

Normal / low aldosterone•CUSHINGS•CAH•LIDDLE’S SYNDROME•APPARENT Mineralocorticoid excess

•HYPERALDOSTERONISM(1’and 2’)

Final DiagnosisFinal Diagnosis

Bartter’s syndrome Bartter’s syndrome Probably Probably type Vtype V (d/t co (d/t co existing Hypocalcemia)existing Hypocalcemia)

BARTTER’S SYNDROMEBARTTER’S SYNDROME

Autosomal recessiveAutosomal recessiveFn of thick ascending LOH affectedFn of thick ascending LOH affected Inactivating mutations of one of 4 Inactivating mutations of one of 4

genes encoding membrane proteins genes encoding membrane proteins (Types I to IV)(Types I to IV)

Gain of function mutation in Gain of function mutation in extracellular Ca ion sensing receptor extracellular Ca ion sensing receptor (CaSR)… variant of Bartter +ing with (CaSR)… variant of Bartter +ing with Hypocalcemia (AD inheritance)Hypocalcemia (AD inheritance)

Bartter’s syndrome typesBartter’s syndrome types

Type IType I : mutation in the gene for Na : mutation in the gene for Na K 2Cl cotrasporter (NKCC2) + on the K 2Cl cotrasporter (NKCC2) + on the apical membrane of LOHapical membrane of LOH

Type IIType II : mutation in the gene for : mutation in the gene for ATP regulated K channel (ROMK)ATP regulated K channel (ROMK)

Type IIIType III : mutation in the basolateral : mutation in the basolateral voltage gated Cl channel (ClC – Kb)voltage gated Cl channel (ClC – Kb)

Type IVType IV : mutation in the BSND : mutation in the BSND protein (barttin) that activates beta protein (barttin) that activates beta subunit for ClC Kb and ClC Ka subunit for ClC Kb and ClC Ka

Type VType V : Gain of function mutation in : Gain of function mutation in the CaSR gene … + with the CaSR gene … + with HypocalcemiaHypocalcemia

……. First four types are autosomal . First four types are autosomal recessive : type V is autosomal recessive : type V is autosomal dominantdominant

Clinical featuresClinical features

Present in antenatal period Present in antenatal period or in neonates( III can + in early or in neonates( III can + in early

childhood)childhood)Antenatal …Antenatal … Polyhydramnios & Preterm labourPolyhydramnios & Preterm labourPostnatal …Postnatal … Polyuria , Polydipsia , FTT ,Growth Polyuria , Polydipsia , FTT ,Growth

retardation , Dehydration , retardation , Dehydration , Nephrocalcinosis (universal in I & II ; Nephrocalcinosis (universal in I & II ; only in 20% of III) , Muscle only in 20% of III) , Muscle weakness , Fatigueweakness , Fatigue

Systemic features include fever, Systemic features include fever, vomiting, diarrhea +… vomiting, diarrhea +…

Probably all are d/t PG mediation Probably all are d/t PG mediation fever can be d/t dehydration fever can be d/t dehydration vomiting d/t hypokalemic paralytic ileus.vomiting d/t hypokalemic paralytic ileus.TYPE IV : Sensorineural deafness TYPE IV : Sensorineural deafness

specific detected as early as 1 month of specific detected as early as 1 month of age : also CRF progression in childhood age : also CRF progression in childhood is commonis common

Biochemical abnormalitiesBiochemical abnormalities

Hypokalemic metabolic alkalosisHypokalemic metabolic alkalosisHyperrenninemic hyperaldosteronismHyperrenninemic hyperaldosteronismNormal blood pressureNormal blood pressure Inappropriate urine excretion of K +Inappropriate urine excretion of K + Inappropriate urine excretion of Cl –Inappropriate urine excretion of Cl –HypercalciuriaHypercalciuriaNormo magnesemiaNormo magnesemiaUrinary PG ^ed in majorityUrinary PG ^ed in majorityBlunted response to loop diureticsBlunted response to loop diuretics

NephrocalcinosisNephrocalcinosis ++ ++ +-+- ++ ++ --

PolyhydramniosPolyhydramnios ++ ++ ++ ++ -- --

FTTFTT ++ ++ ++ ++ -- --

Growth RetardationGrowth Retardation ++ ++ ++ ++ -- --

PolyuriaPolyuria ++ ++ ++ ++ ++ --

PolydipsiaPolydipsia ++ ++ ++ ++ ++ --

Muscle cramps/painMuscle cramps/pain -- -- -- -- ++ +-+-

ChondrocalcinosisChondrocalcinosis -- -- -- -- -- +-+-

SN hearing lossSN hearing loss -- -- -- ++ -- --

HypocalcemiaHypocalcemia -- -- -- -- ++ --

FEATURESFEATURESB B II

B B IIII

B B IIIIII

B B IVIV

B B VV

GMGM

Differential diagnosisDifferential diagnosis1.Gitelman’s syndrome1.Gitelman’s syndrome ( Differentiated by Hypocalciuria + : ( Differentiated by Hypocalciuria + :

Hypomagnesaemia +)Hypomagnesaemia +)

2.Vomiting 2.Vomiting (Differentiated by Urinary Cl < 20 (Differentiated by Urinary Cl < 20

meq/L)meq/L)

3.Abuse of loop diuretics3.Abuse of loop diuretics (H/O drug intake + or assaying the (H/O drug intake + or assaying the

expected drugs in urine) expected drugs in urine)

……. All are observed in older patients . All are observed in older patients

TreatmentTreatment

Restore plasma K to about 3.5 Restore plasma K to about 3.5 mmol/l mmol/l

K+ supplementation / Spironolactone K+ supplementation / Spironolactone / Amiloride/ Amiloride

PG inhibitor like indomethacin 2 PG inhibitor like indomethacin 2 mg/day in divided doses …in infants mg/day in divided doses …in infants have reduced incidence of growth have reduced incidence of growth retardationretardation

Few case reports of Few case reports of adult onset Bartter's adult onset Bartter's

syndromesyndrome

American journal of medicine : vol American journal of medicine : vol 61: issue 1 :198561: issue 1 :1985

A patient with Bartter's syndrome in A patient with Bartter's syndrome in whom the disease was recognized at whom the disease was recognized at 52 years52 years of age has been described of age has been described in…. in….

• Adult onset Bartter diagnosed at Adult onset Bartter diagnosed at the age ofthe age of 40 yrs40 yrs

Korean journal of medicine : vol 10 : Korean journal of medicine : vol 10 : number 4 :1995number 4 :1995

Male who had not been Male who had not been diagnosed as Bartter syndrome diagnosed as Bartter syndrome type IV until type IV until 28 yr28 yr because of a because of a mild clinical manifestation. The mild clinical manifestation. The patient also had congenital patient also had congenital deafnessdeafness. . The Journal of Clinical Endocrinology &

Metabolism : Vol. 88 : Number 2 : 2003

Deaf daughter of consanguineous Deaf daughter of consanguineous parents, who was referred for the parents, who was referred for the first time at the first time at the age of 20age of 20, because , because of refractory hypocalcaemia of refractory hypocalcaemia

Antenatal polyhydramnios +Antenatal polyhydramnios +Polydipsia and polyuria. The patient's Polydipsia and polyuria. The patient's

height and weight reached, height and weight reached, respectively, 165 cm and 70 kgrespectively, 165 cm and 70 kg

Oxford journal of medicine : vol 22 : Oxford journal of medicine : vol 22 :

number 1 : 2006number 1 : 2006

ReferencesReferences

Harrison’s text book of internal Harrison’s text book of internal medicinemedicine

Oxford text book of nephrologyOxford text book of nephrologyBrenner & Rector’s text book of Brenner & Rector’s text book of

nephrologynephrology

APPROACH TO APPROACH TO HYPOKALEMIAHYPOKALEMIA

HYPOKALEMIAHYPOKALEMIAHYPOKALEMIAHYPOKALEMIA

urine potassium < 25 mEq/dayurine potassium < 25 mEq/day urine potassium >30 mEq/dayurine potassium >30 mEq/day

urine potassium < 25 mEq/day

Metabolic acidosis

Acid base status

Normal acid base

• Profound sweating• Prolonged decreased Intake• Vomiting, NG suction ,

remote diuretic use

Lower GI loss

Urinary conservation +Urinary conservation +

urine potassium >30 mEq/day

Metabolic alkalosis Normal acid base Metabolic acidosis

Acid base status

•Post ATN/ post obstructive diuresis•Osmotic diuresis•Gentle diuretic use•Decreased magnesium ions•High dose penicillin•Polydipsia/ diabetes insipidus

•Type 1 RTA•Type 2 RTA•DKA•Amphotericin B•acetazolamide

Urinary conservationUrinary conservation - -