A l d ith t lA l d ith t lA lady with recurrent muscle A lady with recurrent muscle weakness and digital ulcersweakness and digital ulcersweakness and digital ulcersweakness and digital ulcers

Dr. W Lee / Dr. HL TangDr. W Lee / Dr. HL TangRenal TeamRenal Team

Department of Medicine and GeriatricsDepartment of Medicine and GeriatricsDepartment of Medicine and GeriatricsDepartment of Medicine and GeriatricsPrincess Margaret HospitalPrincess Margaret Hospital

HISTORYHISTORYHISTORYHISTORY

YYW F/40YYW F/40-- YYW F/40YYW F/40-- Housewife with 1 childHousewife with 1 childHousewife with 1 childHousewife with 1 child-- Patient diagnosed to have Primary Patient diagnosed to have Primary

Raynaud’s disease in 1996Raynaud’s disease in 1996History of migraineHistory of migraine-- History of migraineHistory of migraine

-- Failed vasodilator therapy and Failed vasodilator therapy and pypysympathectomy sympathectomy M lti l d i i d t di it l lM lti l d i i d t di it l l-- Multiple admissions due to digital ulcersMultiple admissions due to digital ulcers

HISTORYHISTORYHISTORYHISTORY

-- Concerning digital ulcers, she was treated with IVConcerning digital ulcers, she was treated with IVprostaglandinprostaglandinprostaglandinprostaglandin

-- Also history of repeated debridement, skin graft Also history of repeated debridement, skin graft and antibiotic treatmentand antibiotic treatment

-- History of amputation of fingersHistory of amputation of fingersy p gy p g-- FU by Rheumatology teamFU by Rheumatology team

DH h d hl i l hi i i tifDH h d hl i l hi i i tif-- DH: hydroxychloroquine, colchicine, pizotifen, DH: hydroxychloroquine, colchicine, pizotifen, and pantoprazoleand pantoprazole

-- Admitted in Jan 2003Admitted in Jan 2003C l i d f l k d dC l i d f l k d d-- Complained of muscle weakness and on and Complained of muscle weakness and on and off vomitingoff vomiting

-- P/E:P/E:-- P/E:P/E:-- Hydration satisfactoryHydration satisfactory-- Chest: clearChest: clearChest: clearChest: clear-- CVS: HS normal no murmurCVS: HS normal no murmur

BP 130/80 BP 130/80 -- Abd: normalAbd: normal-- NS: power 4/5NS: power 4/5

Jerks normal Jerks normal Babinski downgoingBabinski downgoing

ti i t tti i t tsensation intactsensation intact

Investigation result:Investigation result:

CBP normal CBP normal Na Na 131 mmol/L131 mmol/LKK 2 2 mmol/L2 2 mmol/LK K 2.2 mmol/L2.2 mmol/LUrea Urea 3.6 mmol/L3.6 mmol/LCreatinineCreatinine 66 umol/L66 umol/LCreatinine Creatinine 66 umol/L66 umol/LChloride Chloride 89 mmol/L89 mmol/LGlucoseGlucose 7.6 mmol/L7.6 mmol/LLFT LFT normalnormalpHpH 7.577.57pCOpCO 4 8 kPa4 8 kPapCOpCO22 4.8 kPa4.8 kPapOpO22 13.19 kPa13.19 kPaHCOHCO33 32.8 mmol/L 32.8 mmol/L COCO3 3 3 8 o /3 8 o /BEBE 10.4 mmol/L 10.4 mmol/L

Spot urine: Spot urine: NaNa 22 mmol/L22 mmol/LKK 23.3 mmol/L23.3 mmol/LClCl 24 mmol/L24 mmol/LCreatinineCreatinine 1.48 mmol/L1.48 mmol/L

S l lit 266 l/kS l lit 266 l/kSerum osmolality 266 mmol/kgSerum osmolality 266 mmol/kgUrine osmolality 162 mmol/kgUrine osmolality 162 mmol/kg

Serum Ca 2.66 mmol/LSerum Ca 2.66 mmol/LSerum POSerum PO 0 85 mmol/L0 85 mmol/LSerum POSerum PO4 4 0.85 mmol/L0.85 mmol/LSerum Mg 1.0 mmol/LSerum Mg 1.0 mmol/L

Thyroid function test normalThyroid function test normalCortisol Cortisol 197 nmol/L197 nmol/L

Imp:Imp:pp

Hypokalemia and metabolic alkalosisHypokalemia and metabolic alkalosis

Muscle weakness is likely due to Muscle weakness is likely due to h k l ih k l ihypokalemiahypokalemia

-- She was treated with K supplementShe was treated with K supplement

-- Power normalised after correction of Power normalised after correction of serum K levelserum K level

-- Discharged afterwardsDischarged afterwards

Patient was readmitted again due to Patient was readmitted again due to l kl kmuscle weaknessmuscle weakness

Physical findings similar as beforePhysical findings similar as before

Investigation result:Investigation result:NaNa 133 mmol/L133 mmol/LKK 2 5 mmol/L2 5 mmol/LK K 2.5 mmol/L2.5 mmol/LUrea Urea 3.3 mmol/L3.3 mmol/LCC 56 l/L56 l/LCr Cr 56 umol/L56 umol/LChlorideChloride 95 mmol/L95 mmol/L

HH 7 487 48pH pH 7.487.48pCOpCO22 5.18 kPa5.18 kPa

OO 17 87 kP17 87 kPpOpO22 17.87 kPa17.87 kPaHCOHCO33 28.2 mmol/L28.2 mmol/LBEBE 4 6 l/L4 6 l/LBEBE 4.6 mmol/L4.6 mmol/L

Spot Urine:Spot Urine:Spot Urine: Spot Urine: Na 67 mmol/LNa 67 mmol/LK 21.6 mmol/LK 21.6 mmol/LCl 57 mmol/LCl 57 mmol/L

S l li 261 l/kS l li 261 l/kSerum osmolality 261 mmol/kgSerum osmolality 261 mmol/kgUrine osmolality 254 mmol/kgUrine osmolality 254 mmol/kg

24 hr urine: 24 hr urine: Na 323 mmol/24hrNa 323 mmol/24hrK 84.2 mmol/24hrK 84.2 mmol/24hr

S C 2 35 l/LS C 2 35 l/LSerum Ca 2.35 mmol/LSerum Ca 2.35 mmol/LSerum POSerum PO44 0.54 mmol/L0.54 mmol/LSerum Mg 0 92 mmol/LSerum Mg 0 92 mmol/LSerum Mg 0.92 mmol/LSerum Mg 0.92 mmol/L

Differential Diagnosis andDifferential Diagnosis andDifferential Diagnosis and Differential Diagnosis and what further tests will you order?what further tests will you order?

Differential Diagnosis of unexplained Differential Diagnosis of unexplained Metabolic Alkalosis and HypokalemiaMetabolic Alkalosis and Hypokalemiaypyp

1. Surreptitious, self-induced vomiting

2. Diuretic abuse

3. Gitelman’s or Bartter’s syndrome

- 24 hr urine Ca : 4.08 ( 2.5 -7.5 mmol/24 hr)- 24 hr urine PO4: 10.27 (15-50 mmol/24 hr)- 24 hr urine for Total protein < 0.06 gm per day- MSU: R/M normal, no cast

- Renin: supine 2 2 ( 0 68-1 36 ng/ml/hr)supine 2.2 ( 0.68 1.36 ng/ml/hr)erect 4.1 ( 0.24-4.7 ng/ml/hr)

- Aldosterone:i 151 ( 28 444 l/L)supine 151 ( 28-444 pmol/L)

erect 251 ( 111-860 pmol/L)

Other problemsOther problemsOther problemsOther problems

2001: PUO2001: PUO-- Gallium scan: abnormal uptake at smallGallium scan: abnormal uptake at small-- Gallium scan: abnormal uptake at smallGallium scan: abnormal uptake at small

and large bowelsand large bowels-- Colonoscopy: colitisColonoscopy: colitis

Colonic biopsy: melanosis coliColonic biopsy: melanosis coli-- Colonic biopsy: melanosis coliColonic biopsy: melanosis coli

Other problemsOther problems

-- Recurrent calf and feet abscessRecurrent calf and feet abscessRecurrent calf and feet abscess Recurrent calf and feet abscess requiring repeated incision and drainage, requiring repeated incision and drainage, d b id t d ki ftd b id t d ki ftdebridement and skin graftdebridement and skin graft

-- Wound swabs: multiple coliform bacteriaWound swabs: multiple coliform bacteriaand gram negative bacilli including and gram negative bacilli including Klebsiella E coli and enterobacterKlebsiella E coli and enterobacterKlebsiella, E. coli and enterobacterKlebsiella, E. coli and enterobacter

-- History of enterobacter septicemiaHistory of enterobacter septicemia

- ?? Factitious Disorder ?? Factitious Disorder ac ous so deac ous so de

-- ?? Drug abuse?? Drug abuse

-- ?? Self?? Self--inflicted woundsinflicted wounds

Urine toxicology by HPLC:Urine toxicology by HPLC:Urine toxicology by HPLC:Urine toxicology by HPLC:

E h d i / d h d i f id dE h d i / d h d i f id d-- Ephedrine/pseudoephedrine, frusemide andEphedrine/pseudoephedrine, frusemide andchloroquine were detectedchloroquine were detected

-- On further enquiry, patient admitted that sheOn further enquiry, patient admitted that shetook herbal tea (took herbal tea (苦丁茶苦丁茶))

-- Herbal tea was sent for toxicology screening:Herbal tea was sent for toxicology screening:no frusemide detectedno frusemide detectedno frusemide detectedno frusemide detected

Progress:Progress:

-- Patient was advised to stop all those herbal teaPatient was advised to stop all those herbal teaand any private drug and any private drug

-- During FU: K still on low side despite on KDuring FU: K still on low side despite on Ksupplementsupplement

-- Lowest K level 1.8 mmol/L, requiring multiple Lowest K level 1.8 mmol/L, requiring multiple admissions for managementadmissions for management

-- Urine for toxicology ( LCUrine for toxicology ( LC--MS) repeated:MS) repeated:Frusemide, hydrochlorothiazide and triamtereneFrusemide, hydrochlorothiazide and triamterene

On repeated enquiry, patient admitted On repeated enquiry, patient admitted that she took herbal laxative (that she took herbal laxative (審瀉審瀉葉葉))that she took herbal laxative (that she took herbal laxative (審瀉審瀉葉葉))

? Any other drug intake or herbs intake? Any other drug intake or herbs intake

Strongly advised her to stop all those Strongly advised her to stop all those herbs or any private drugherbs or any private drugherbs or any private drugherbs or any private drug

Summary:Summary:

-- A young lady with history of Raynaud’s disease,A young lady with history of Raynaud’s disease,recurrent digital ulcers and require surgicalrecurrent digital ulcers and require surgicalinterventionintervention

-- Recurrent muscle weakness secondary to Recurrent muscle weakness secondary to hypokalemiahypokalemiahypokalemiahypokalemia

-- Hypokalemia is due to diuretic abuseHypokalemia is due to diuretic abusefrusemidefrusemide. frusemide. frusemide

. hydrochlorothiazide + triamterene. hydrochlorothiazide + triamterene? Dyazide or apo? Dyazide or apo triazidetriazide? Dyazide or apo? Dyazide or apo--triazidetriazide

-- Laxative abuse ( herbal laxative)Laxative abuse ( herbal laxative)? Self? Self inflicted wounds/abscessesinflicted wounds/abscesses-- ? Self? Self--inflicted wounds/abscesses inflicted wounds/abscesses

Factitious disorder / Munchausen Syndrome

Refer to Psychiatrist for assessment and– Refer to Psychiatrist for assessment andfurther management

Potassium physiologyPotassium physiology

-- ICF contains 98% of KICF contains 98% of K++ in the bodyin the bodyICF contains 98% of KICF contains 98% of K in the bodyin the body-- ICF [KICF [K++] 35 to 40 fold greater than that in ECF] 35 to 40 fold greater than that in ECF-- Clinical importance of KClinical importance of K++ is that any surplus oris that any surplus or-- Clinical importance of KClinical importance of K is that any surplus oris that any surplus or

deficit may predispose the patient to cardiacdeficit may predispose the patient to cardiacarrhythymiaarrhythymiaarrhythymiaarrhythymia

-- The kidney adjust overall KThe kidney adjust overall K++ hemostasishemostasish h i f Kh h i f Kthrough excretion of Kthrough excretion of K++

Physiology of KPhysiology of K++ excretionexcretionPhysiology of KPhysiology of K excretionexcretion

-- Events controlling KEvents controlling K++ excretion have their excretion have their greatest impact in the CCDgreatest impact in the CCDg pg p

-- The major type of cell involved is the The major type of cell involved is the principal cellprincipal cellprincipal cellprincipal cell

-- KK++ excretion = urine [Kexcretion = urine [K++ ] X urine volume] X urine volume

Causes of hypokalemiaCauses of hypokalemiaypyp

1. Decreased intake1. Decreased intake2. Redistribution into cells2. Redistribution into cells2. Redistribution into cells2. Redistribution into cells3. Increased loss:3. Increased loss:

renal renal nonnon--renal: gastrointestinal sweatrenal: gastrointestinal sweatnonnon renal: gastrointestinal ,sweatrenal: gastrointestinal ,sweat

1) 1) Decreased intakeDecreased intake

-- Normal range of K intake is 40Normal range of K intake is 40 –– 120120 mmolmmol perper-- Normal range of K intake is 40 Normal range of K intake is 40 –– 120 120 mmolmmol perperdayday, most , most of which is then excreted in the urineof which is then excreted in the urine

-- Kidney is able to lower K excretion to a minimum Kidney is able to lower K excretion to a minimum of 5of 5--25mmol per day in presence of K depletion25mmol per day in presence of K depletion

-- Decreased intake alone rarely cause Decreased intake alone rarely cause hypokalemiahypokalemia

-- However it can contribute to the severity of KHowever it can contribute to the severity of Kdepletion when another problem isdepletion when another problem isdepletion when another problem is depletion when another problem is superimposed such as diuretic therapysuperimposed such as diuretic therapy

2)2) Increased entry into cellsIncreased entry into cells)) yy

-- metabolic alkalosismetabolic alkalosismetabolic alkalosismetabolic alkalosis-- increased availability of insulinincreased availability of insulin

elevated beta adrenergic activityelevated beta adrenergic activity-- elevated beta adrenergic activityelevated beta adrenergic activity-- hypokalemic periodic paralysishypokalemic periodic paralysis-- marked increase in blood cell productionmarked increase in blood cell production-- hypothermiahypothermiaypyp-- barium intoxicationbarium intoxication

3) 3) Increased GI lossIncreased GI loss

loss of gastric or intestinal secretionsloss of gastric or intestinal secretionsloss of gastric or intestinal secretions loss of gastric or intestinal secretions from any cause( vomiting, diarrhoea, from any cause( vomiting, diarrhoea, laxative or tube drainage)laxative or tube drainage)laxative or tube drainage)laxative or tube drainage)

4) 4) Increased urine lossIncreased urine loss))

-- diureticdiuretic-- diureticdiuretic-- primary mineralocorticoid excessprimary mineralocorticoid excess

loss of gastric secretionsloss of gastric secretions-- loss of gastric secretionsloss of gastric secretions-- nonreabsorbable anionsnonreabsorbable anions

t b li id it b li id i-- metabolic acidosismetabolic acidosis-- hypomagnesemiahypomagnesemia-- amphotericin Bamphotericin B-- salt wasting nephropathysalt wasting nephropathyg p p yg p p y-- polyuria polyuria

Manifestations of hypokalemiaManifestations of hypokalemiaManifestations of hypokalemiaManifestations of hypokalemia

1) Severe muscle weakness or paralysis2) Cardiac arrhythymia and ECG abnormalities) y y3) Rhabdomyolysis4) Renal abnormalities4) Renal abnormalities

Hypokalemia-induced renal dysfunction

1) Impaired urinary concentration1) Impaired urinary concentration2) Increased renal ammonia production3) Enhanced bicarbonate reabsorption4) Altered sodium reabsorption4) Altered sodium reabsorption5) Hypokalemic nephropathy

Approach to HypokalemiaApproach to Hypokalemia- Hypokalemia is a common clinical problem

- Evaluation of intake, distribution and excretion of potassium by:p y

• History taking ( ? Diuretic use, vomiting or y g ( , gdiarrhoea)

• physical examination including blood p y gpressure and orthostatic changes in blood pressure and heart ratep

• urine and plasma electrolyte and osmolality• arterial blood gasg

Approach to HypokalemiaApproach to Hypokalemia

- Useful test to monitor the urinary potassiumUseful test to monitor the urinary potassium excretion include:

a) 24 hr urine potassium excretion rate< 15 mmol/day in the presence ofyhypokalemia of extrarenal etiology

b) spot urine for [potassium] to [creatinine] ratio)< 1 in presence of hypokalemia of extrarenaletiology

c) Transtubular potassium gradient ( TTKG)

Transtubular K+ gradient (TTKG)Transtubular K+ gradient (TTKG)

-- Estimate the degree of aldosterone activity byEstimate the degree of aldosterone activity bymeasuring of tubular fluid K conc at the end ofmeasuring of tubular fluid K conc at the end ofcortical collecting tubule, the site responsible for cortical collecting tubule, the site responsible for most of K secretionmost of K secretion

-- Dependent upon 2 assumptions:Dependent upon 2 assumptions:• urine osmolality at the end of cortical collecting

tubule is similar to that of plasma• little or no K secretion or reabsorption in the

medullary collecting tubule

TTKG= [ Urine K /(urine osmolality/plasma osmolality)]/plasma KTTKG= [ Urine K /(urine osmolality/plasma osmolality)]/plasma K

urine osmolality exceeds that of plasmaurine osmolality exceeds that of plasmaurine Na conc > 25 mmol/Lurine Na conc > 25 mmol/L

In h pokalemia patientIn h pokalemia patientIn hypokalemia patient:In hypokalemia patient:

TTKG

Factitious disorder / Munchausen Syndrome

-- Factitious disorder is one form of feigned illnessFactitious disorder is one form of feigned illness

y

gg-- DDefining characteristics are:efining characteristics are:

1. Intentional production of feigned physical orpsychological signs or symptoms

2. Presence of illness behavior reflecting a wish to assume the sick rolethe sick role

3. Confronting physicians with self-induced symptoms or disease

4. Absence of external incentives for the behavior (eg, economic gain, avoiding legal responsibility, or improving general wellbeing as in malingering)general wellbeing as in malingering)

-- Treatment:Treatment:Treatment:Treatment:- No specific therapy- Core management should include:Core management should include:

1. Treatment of self-induced medical or surgical conditions, as indicated

2. Education of medical/surgical staff regarding illness behavior and dynamics in factitia, to reduce the clinician’s feelings of anger, frustration, and g g , ,helplessness

3. Protecting the patient from self-harm or harmful proceduresprocedures

4. Attempting to limit a patient’s care to one primary physician and hospital

Latest progress of our patientLatest progress of our patient

July 08:July 08:NaNa 138 mmol/L138 mmol/LKK 3.1 mmol/L3.1 mmol/LUreaUrea 5 4 mmol/L5 4 mmol/LUreaUrea 5.4 mmol/L5.4 mmol/LCreatinineCreatinine 53 umol/L53 umol/L

Taking slow K 1200 mg tds poTaking slow K 1200 mg tds poTaking slow K 1200 mg tds poTaking slow K 1200 mg tds po

• Urine toxicology screening by LC-MS: – Frusemide, hydrochlorothiazide, triamterene , y ,

were still detected

• The laboratory findings are consistent with titi f di tisurreptitious use of diuretics

Thank youThank youThank youThank you