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2011/4/6 Jesus Loves You! Electrolytes Part II Potassium Dr Chloe Mak MBBS, PhD, FRCPA, FHKCPA, FHKAM Consultant Chemical Pathologist Princess Margaret Hospital [email protected]
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  • 2011/4/6 Jesus Loves You!

    Electrolytes Part II Potassium

    Dr Chloe MakMBBS, PhD, FRCPA, FHKCPA, FHKAM

    Consultant Chemical PathologistPrincess Margaret Hospital

    [email protected]

  • 2011/4/6 Jesus Loves You!

    Homeostasis

    Input: In diet, e.g. meat, fish, fruit

    Distribution Mainly in intracellular compartment

    Output Body fluids with varying K concentrations See Table

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    Hyperkalemia Defined as

    plasma K >5.0 mmol/L, or, serum K >5.5 mmol/L

    Consequences of hyperkalemia: Mild: non-specific: malaise, vomit, nausea Vague muscle weakness (first sign) Flaccid paralysis Paraesthesia No correlation between weakness & K Cardiac arrhythmia

    ECG changes: 6-7mmol/L: tall, peaked T waves 8-10mmol/L: aberrant QRS complexes 11mmol/L: fusion of QRS and T waves 10-12mmol/L: ventricular fibrillation

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    Prostaglandin inhibitionIndomethacinDiabetes MellitusInterstitial nephritis Syndrome of hyporeninemic hypoaldosteronismCommon in elderly with DM and mild renal impairment

    Mineralocorticoid resistance(2 hyperaldosteronism)Interstitial nephritisObstructive uropathyAmyloidosisSLEPseudohypoaldosteronism

    Extrarenal causes

    Renin Aldosterone

    Renin Aldosterone

    Spot Renin & Aldosterone

    ACTH stimulation

    Plasma creatinine

    Plasma HCO-3-

    Exclude

    Selective aldosterone deficiency

    Addisons diseaseC21- -Hydroxylase deficiency

    Normal response

    No response/Blunted response

    Normal

    High Renal Failure (Acute or end stage renal failure)

    Anion GapNormal

    Decreased

    NormalIncreased

    DKARenal failure

    *Extrarenal causes: Pseudohyperkalemia (eg hemolysed specimen, EDTA contamination, thrombocytosis, leucocytosis, aged samples) , tumor lysis syndrome, tissue necrosis, periodic paralysis hyperkalemia, drugs: IV/oral K therapy Acute renal failure Repeat K once

    Renin Aldosterone

    Normal Renin & Aldosterone

    Hyperkalemia

    Source: Cases in Chemical Pathology, RN Walmsley

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    Diagnostic Approach Hyperkalemia noted in the laboratory report R/o factitious results like:

    Hemolysis Thrombocytosis Leucocytosis EDTA contamination Drip-arm

    Repeat sample if query Decide the severity

    Moderate: 6.5mmol/L

    Do an ECG (save Urine K +/- other blood samples before Tx) Give treatment accordingly Review the test profiles for ? RF, ? DKA

    Review drug history, K-sparing diuretics, oral intake

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    Extracellular Intracellular Distribution

    1. Na/K ATPase Pump 2. Acid-base 3. Insulin 4. Adrenaline

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    Extracellular Intracellular Distribution

    1. Na/K ATPase Pump

    If the pump fails, what will happen? What can cause the pump to fail?

    www.cvphysiology.com

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    Case 1

    F/65y, HT, DM. OPD FU Collection time 15/4/2011 14:05 Arrival time 16/4/2011 10:13 Plasma Na 140 (132-144mmol/L) K 5.5 (3.2-4.8mmol/L) Urea 5 (3.0-8.0mmol/L) Cr 125 (60-120umol/L)

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    2. Acid-base status HyperK and acidosis HypoK and alkalosis

    Extracellular Intracellular Distribution

    Ref: mgwater.com

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    Case 2

    F/65y Plasma Na 140 (132-144mmol/L) K 5.5 (3.2-4.8mmol/L) HCO3 15 (23-28 mmol/L) Urea 5 (3.0-8.0mmol/L) Cr 100 (60-120umol/L)

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    3. Insulin Insulin promotes cellular uptake of

    Glucose Potassium magnesium phosphate

    Extracellular Intracellular Distribution

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    Case 3a

    F/65y, nonketotic hyperglycemia, insulin drip was given

    Insulin drip must be given together with _____!!!

    To avoid lethal hypokalemia!

    uwhealth.org

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    Case 3b M/48, known DM, found LOC Plasma Na 132 (132-144mmol/L) K 6.5 (3.2-4.8mmol/L) Urea 23 (3.0-8.0mmol/L) Cr 323 (60-120umol/L) Glucose 18 mmol/L Urine ketone ++ Potassium deficit despite hyperkalaemia

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    4. Adrenaline Adrenaline stimulates cellular potassium

    uptake Lead to HypoK

    Extracellular Intracellular Distribution

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    Case 4

    M/45y, asthma on ventolin, suicide attempt by drug overdose

    Plasma Na 140 (132-144mmol/L) K 2.8 (3.2-4.8mmol/L) Urea 5 (3.0-8.0mmol/L) Cr 100 (60-120umol/L)

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    Renal Potassium Excretion

    Aldosterone action

    Na+

    K+

    H+

    Lumen Collecting ducts Blood

    Aldosterone

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    Case 5 Too less aldosterone Baby / 1 day old, ambiguous external

    genitalia, hypotensive Plasma Na 118 (132-144mmol/L) K 6.5 (3.2-4.8mmol/L) Urea 9.5 (3.0-8.0mmol/L) Cr 60 (30-50umol/L)

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    http://www.aafp.org/afp/990301ap/1190.html

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    Some Types of Congential Adrenal Hyperplasia

    Frequency %

    Mineralocorticoids Androgens

    21-hydroxylase CAH 90-95% 11-hydroxylase CAH 5% 3-HSD CAH very rare 17-hydroxylase CAH very rare

    Wikipedia

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    Case 6 Too much aldosterone F/39y, young onset of hypertension

    Plasma Na 143 (132-144mmol/L) K 3.0 (3.2-4.8mmol/L) Urea 5.0 (3.0-8.0mmol/L) Cr 70 (60-120umol/L)

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    Cause: Factitious Hyperkalemia

    Plasma or serum K higher? Release of K from platelets in clotting

    Leucocytosis Thrombocytosis Hemolysis

    Increased Intracellular constituents E.g. AST, LDH, urate

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    Case 7a M/70y, CRF with renal transplant 10 years

    ago, FU OPD

    Na 140 (132-144mmol/L) K 9.5 (3.2-4.8mmol/L) Urea 5 (3.0-8.0mmol/L) Cr 110 (60-120umol/L)

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    Case 7a K 9.5 mmol/L is life-threatening unlikely to be true in normal individuals In addition, the patients RFT was normal. Suspected artifact

    Ca 0.56 (2.20-2.60mmol/L)

    EDTA contamination

    What else will be falsely abnormal?

    Do ECG if in doubt

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    Case 7b M/27, leukemia, just post chemotherapy Na 140 (132-144mmol/L) K 9.5 (3.2-4.8mmol/L) Urea 5 (3.0-8.0mmol/L) Cr 125 (60-120umol/L) Ca 0.56 (2.20-2.60mmol/L)

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    Case 7b

    High PO4, urate Tumour lysis syndrome

    Tissue damage: High K, PO4, AST, LDH, uric acid Tumor lysis Syndrome Other causes: trauma, burns, rhabdomyolysis

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    Case 7c M/58, Plasma Na 140 (132-144mmol/L) K 6.5 (3.2-4.8mmol/L) Urea 5 (3.0-8.0mmol/L) Cr 100 (60-120umol/L)Comments: Sample hemolyzed.

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    In general, marked hemolysis produces misleading results in the following analytes:

    Can increase: Phosphate, potassium (horses, pigs, Japanese breed dogs (e.g. Akitas), some cows and sheep), CK, AST, LDH, uric acid, and magnesium.

    Can decrease: alkaline phosphatase, amylase, and GGT.

    http://ahdc.vet.cornell.edu/clinpath/modules/chem/hemol.htm

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    Case 8 You noted that the values of K are different in different sample

    types for different tests. The three samples are collected on the same time. why?

    Patient A

    K from ABG profile using whole blood sample

    6.8

    Plasma K 4.4Serum K 4.9

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    Digitalis

    Inhibit Na/K ATPase pump Inhibit intracellular K+ uptake

    Digoxin overdose hyperK

    Risk factors for digoxin overdose: Elderly Hypothyroidism HypoK

    with courtesy of Dr Morris Tai

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    Internal balance

    3Na+

    2K+Digoxin

    glucose

    K+

    insulin

    Catecholamines, aldosterone, thyroxine

    H+H+K+

    K+

    with courtesy of Dr Morris Tai

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    Autosomal dominant disorder Acute onset of muscle weakness

    associated with hyperK Spontaneously resolves over a few hrs PPt by exercise, cold, hyperK

    Hyperkalemic periodic paralysis

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    AD mode Male predominance Attacks of flaccid paralysis lasting 6-24

    hours with marked hypoK Spontaneously return to normoK

    afterwards

    Hypokalamic periodic paralysis

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    Case 8 M/18y, sudden onset of paralysis Plasma Na 140 (132-144mmol/L) K 5.5 (3.2-4.8mmol/L) Urea 5 (3.0-8.0mmol/L) Cr 100 (60-120umol/L)

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    Common causes of hyperkalaemia

    1. Artefactual2. Renal failure3. K-sparing diuretics

    Medically important causes of hyperkalaemia

    1. Mineralcorticoid deficiency Some types of congenital adrenal hyperplasma Addisons disease

    2. DKA (apparent hyperK)

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    HypoK

    Defined as plasma K

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    Inadequate intakeChronic alcoholismAnorexia nervosaInappropriate IV therapyExtrarenal lossChronic diarrheaLaxative abusePrevious diureticsVillous adenoma of colonSalbutamol, insulinHypokalemic periodicParalysisIntracellular shift vitamin B12 therapy

    Renal Loss VomitingCurrent diureticsMineralocorticoid excess syndromeGentamycinMg depletion ( can cause refractory hypocalcemia & hypokalemia) Leukemia

    Acute diarrhea

    Renal LossRenal tubular acidosis type 1, type 2Carbonic anhydrase inhibitors

    < 20 40 mmol/L

    Plasma HCO3-

    Normal/ Increased

    Decreased

    Paired Spot urine K before K replacement

    > 20 40 mmol/L

    Paired spot Urine K before K replacement

    < 20 40 mmol/L

    > 20 40 mmol/L

    Hypokalemia Diagnostic Pathway of Hypokalemia

    Source: Cases in Chemical Pathology, RN Walmsley

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    Common causes of hypokalaemia1. Diuretics2. Vomiting/diarrhoea3. Magnesium deficiency

    Medically important causes of hypokalaemia1. Mineralcortcoid excess 2. Glucocorticoid excess3. Renal tubular acidosis

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    Table: Approximate electrolyte composition of body fluids:

    Concentration (mmol/L)Na+ K+ Cl- HCO3-

    Plasma 140 4 100 25Saliva 60 15 30 40Gastric Juice 80 10 150 --Bile 150 10 50 30Pancreatic 110 10 40 100Diarrhoea fluid 60 40 ~ 100 varied variedUrine 100 50 80 --

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    Case 9 M/3mo, pyloric stenosis with refractory vomiting

    Plasma Na 140 (132-144mmol/L) K 2.5 (3.2-4.8mmol/L) HCO3 30 (23-28 mmol/L) Urea 5 (3.0-8.0mmol/L) Cr 100 (60-120umol/L)

    Vomiting Alkalosis potentiate hypoK Secondary hyperaldosteronism if hypovolemia

    Similar mechanisms in excessive nasogastric suction

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    Case 10

    M/65, chronic smoker, weight loss and dry cough for 3 months

    Na 140 (132-144mmol/L) K 2.6 (3.2-4.8mmol/L) Urea 7 (3.0-8.0mmol/L) Cr 110 (60-120umol/L)

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    Case 10

    Further investigations Urine K = 102 mmol/l

    Cortisol 2424 umol/L ACTH increased

    CXR lung mass Dx?

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    Case 11 F/70y, ca stomach on chemotherapy Plasma K 2.3 mmol/L (3.5-5.0) Ca 1.86 mmol/L (2.25-2.55) PO4 0.56 mmol/L (0.6-1.2) ALB 30 g/L (30-52)

    Hypocalcemia refractory to replacement Whats the reason for his hypocalcemia?

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    Hypomagnesemia

    Severe hypomagnesemia

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    Prostaglandin inhibitionIndomethacinDiabetes MellitusInterstitial nephritis Syndrome of hyporeninemic hypoaldosteronism(Common in elderly with DM and mild renal impairment )

    Mineralocorticoid resistance(2 hyperaldosteronism)Interstitial nephritisObstructive uropathyAmyloidosisSLEPseudohypoaldosteronism

    Extrarenal causes

    Renin Aldosterone

    Renin Aldosterone

    Spot Renin & Aldosterone

    ACTH stimulation

    Plasma creatinine

    Plasma HCO-3-

    Exclude

    Selective aldosterone deficiency

    Addisons diseaseC21- -Hydroxylase deficiency

    Normal response

    No response/Blunted response

    Normal

    High Renal Failure (Acute or end stage renal failure)

    Anion GapNormal

    Decreased

    NormalIncreased

    DKARenal failure

    *Extrarenal causes: Pseudohyperkalemia (eg hemolysed specimen, EDTA contamination, thrombocytosis, leucocytosis, aged samples) , tumor lysis syndrome, tissue necrosis, periodic paralysis hyperkalemia, drugs: IV/oral K therapy Acute renal failure Repeat K once

    Renin Aldosterone

    Normal Renin & Aldosterone

    Hyperkalemia

    Source: Cases in Chemical Pathology, RN Walmsley

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    Try to practice in this way: Make up a case of Syndrome of hyporeninemic

    hypoaldosteronism Common in elderly with DM and mild renal impairment Hx: ____________________ Na ____ (132-144mmol/L) K ____ (3.2-4.8mmol/L) Urea ____ (3.0-8.0mmol/L) Cr ____ (60-120umol/L)

    What other investigations do I need? ___________________

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    Inadequate intakeChronic alcoholismAnorexia nervosaInappropriate IV therapyExtrarenal lossChronic diarrheaLaxative abusePrevious diureticsVillous adenoma of colonSalbutamol, insulinHypokalemic periodicParalysisIntracellular shift vitamin B12 therapy

    Renal Loss VomitingCurrent diureticsMineralocorticoid excess syndromeGentamycinMg depletion ( can cause refractory hypocalcemia & hypokalemia) Leukemia

    Acute diarrhea

    Renal LossRenal tubular acidosis type 1, type 2Carbonic anhydrase inhibitors

    < 20 40 mmol/L

    Plasma HCO3-

    Normal/ Increased

    Decreased

    Paired Spot urine K before K replacement

    > 20 40 mmol/L

    Paired spot Urine K before K replacement

    < 20 40 mmol/L

    > 20 40 mmol/L

    Hypokalemia Diagnostic Pathway of Hypokalemia

    Source: Cases in Chemical Pathology, RN Walmsley

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    Try to practice in this way: Make up a case of Renal tubular acidosis type 1 Hx: ____________________ Na ____ (132-144mmol/L) K ____ (3.2-4.8mmol/L) Urea ____ (3.0-8.0mmol/L) Cr ____ (60-120umol/L)

    What other investigations do I need? ___________________

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    Thank you

    Electrolytes Part IIPotassiumHomeostasisHyperkalemia 4Diagnostic ApproachExtracellular Intracellular DistributionExtracellular Intracellular DistributionCase 1Extracellular Intracellular DistributionCase 2Extracellular Intracellular DistributionCase 3aCase 3bExtracellular Intracellular DistributionCase 4Renal Potassium ExcretionCase 5 Too less aldosterone 18 19Case 6 Too much aldosteroneCause: Factitious HyperkalemiaCase 7aCase 7a Case 7bCase 7bCase 7c 27Case 8DigitalisInternal balance 31Hypokalamic periodic paralysisCase 8 34HypoK 36 37Table: Approximate electrolyte composition of body fluids:Case 9Case 10Case 10Case 11Hypomagnesemia 44Try to practice in this way: 46Try to practice in this way:Thank you