Elettroliti e CUOREElettroliti e CUORE

Stefano Nardi, MD, PhD Stefano Nardi, MD, PhD

AZIENDA OSPEDALIERA SANTA MARIA, TERNIAZIENDA OSPEDALIERA SANTA MARIA, TERNI DIPARTIMENTO CARDIOTORACOVASCOLARE DIPARTIMENTO CARDIOTORACOVASCOLARE

STRUTTURA COMPLESSA DI CARDIOLOGIA STRUTTURA COMPLESSA DI CARDIOLOGIA

CENTRO DI ARITMOLOGIA CLINICA ED CENTRO DI ARITMOLOGIA CLINICA ED ELETTROFISIOLOGIA CARDIACAELETTROFISIOLOGIA CARDIACA

LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONELABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE

.....chiara.........chiara....

Parlare di tutto.......

......in maniera approfondita,

...ed in poco tempo!!!!

Missione impossibileMissione impossibile

HH22O & Electrolytes distributionO & Electrolytes distribution Non-electrolytesNon-electrolytes

– formed by only covalent bondsformed by only covalent bonds– do not form charged ions in solution do not form charged ions in solution

ElectrolytesElectrolytes– formed with some ionic bonds; formed with some ionic bonds; – Dissociate into (+) & (-) in Dissociate into (+) & (-) in

solutions solutions (acids, bases, salts)(acids, bases, salts)– 4 important physiological 4 important physiological

functions in the bodyfunctions in the body essential minerals in certain essential minerals in certain

biochemical reactionsbiochemical reactions CTR Posm = CTR movement of CTR Posm = CTR movement of

water between compartmentswater between compartments maintain acid-base balancemaintain acid-base balance

conduct electrical currents conduct electrical currents (depolarization events)(depolarization events)

Some Electrolyte Reference Some Electrolyte Reference Ranges and Units (HVA)Ranges and Units (HVA)

Sodium:Sodium: 136-142 mEq/L136-142 mEq/L Clorum:Clorum: 95-103 mEq/L95-103 mEq/L Potassium: Potassium: 3.5 – 5.1 mEq/L3.5 – 5.1 mEq/L Magnesium:Magnesium: 1.8 – 2.4 mg/dL1.8 – 2.4 mg/dL Phosphorus:Phosphorus: 2.5 – 4.5 mg/dL2.5 – 4.5 mg/dL Calcium:Calcium: 8.5 – 10.5 mg/dL8.5 – 10.5 mg/dL

Electrolytes (ECF)Electrolytes (ECF) NaNa++ (136-142 mEq/L) (136-142 mEq/L)

– Most abundant cationMost abundant cation major ECF cation (90%)major ECF cation (90%) determines Posm ECFdetermines Posm ECF

– RegulationRegulation AldosteroneAldosterone ADHADH ANPANP

ClCl-- (95-103 mEq/L) (95-103 mEq/L) – Major ECF anionMajor ECF anion

helps balance osmotic potential and electrostatic helps balance osmotic potential and electrostatic equilibrium between fluid compartments equilibrium between fluid compartments

plasma membranes tend to be leaky to Clplasma membranes tend to be leaky to Cl-- anions anions– Regulation: aldosterone Regulation: aldosterone

K+K+

K+

K+

_

_ _

_

_

Na+Na+

Na+Na+

Cl-

Cl-

Cl-

Cl-Cl-

Cl-

Potassium (KPotassium (K++)) – Major ICF cationMajor ICF cation

intracellular 120-125 mEq/literintracellular 120-125 mEq/liter plasma 3.8-5.0 mEq/literplasma 3.8-5.0 mEq/liter

Calcium (CaCalcium (Ca2+2+))– Most abundant ion in bodyMost abundant ion in body

plasma 4.6-5.5 mEq/liter plasma 4.6-5.5 mEq/liter most stored in bone (98%)most stored in bone (98%)

Magnesium (MgMagnesium (Mg2+2+))– 22ndnd most abundant ICF cation most abundant ICF cation

1.3-2.1 mEq/liter in plasma 1.3-2.1 mEq/liter in plasma more than half stored in bone, more than half stored in bone,

most of the rest in ICF most of the rest in ICF

Electrolytes (ICF)Electrolytes (ICF)

Electrolytes (ICF)Electrolytes (ICF) Potassium (KPotassium (K++))

– Role in resting membrane potential and in APRole in resting membrane potential and in AP– Regulation:Regulation:

Direct Effect: excretion by kidney tubule Direct Effect: excretion by kidney tubule AldosteroneAldosterone

Calcium (CaCalcium (Ca2+2+))– Regulation:Regulation:

Parathyroid Hormone (PTH) - Parathyroid Hormone (PTH) - ↑↑ blood Ca blood Ca2+2+

Calcitonin (CT) - Calcitonin (CT) - ↓↓ blood Ca blood Ca2+2+

Magnesium (MgMagnesium (Mg2+2+))– Regulation:Regulation:

important enzyme cofactor; involved in neuromuscular activity, important enzyme cofactor; involved in neuromuscular activity, nerve transmission in CNS, and nerve transmission in CNS, and myocardial functioningmyocardial functioning

0.9% NaCl

3% NaCl

0.9% NaCl

0.5% NaCl

Hypotonic vs HypertonicHypotonic vs Hypertonic

Water and Electrolyte balanceWater and Electrolyte balance

IPERTONICITÀ IPOTONICITÀ

Osmocettori ipotalamici attivati

Osmocettori ipotalamici inibiti

↑sete ↓sete

↑ LiberazioneADH

↓ LiberazioneADH

↑ Apporto idrico ↓ Apporto idrico

Diuresi contratta Diuresi aumentata

(2x[Na+] ) + BUN(mg/dl) + glucosio(mg/dl)2,8 18

Electrolyte BalanceElectrolyte Balance

Riduzione del margine di errore per il mantenimento dell’equilibrio elettrolitico normale (tachipnea, perdite Renali e GI)

What’s happened in Eldery ptsWhat’s happened in Eldery pts

Riduzione NEFRONI Risposta alla sete più tardiva e meno intensa Ridotta capacità di concentrazione Urine

What’s happened in Eldery ptsWhat’s happened in Eldery pts

• Livelli ematici ANP aumentati (inibisce RAA)

• Compromissione meccanismi di conservazione H20 e alterazione bilancio del Na+ con bilancio negativo (riduzione livelli circolanti RAA)

• Resistenza renale all’azione dell’ADH

(diabete insipito nefrogeno parziale) • SIADH (cardiopatie, epatopatie, nefropatie croniche)

• Alterazione emodinamici (SV, BP, FPR; VFG, NS)

Rhythm Basics OverviewRhythm Basics Overview

Electrolytes can affect the Electrolytes can affect the Conduction SystemConduction System– Cardiac FunctionCardiac Function– Action PotentialAction Potential– Impulse FormationImpulse Formation– Impulse Conduction Impulse Conduction

Three types of homeostasis are involved in the Three types of homeostasis are involved in the maintenance of normal volume and normal maintenance of normal volume and normal composition of ECG:fluid balance, electrolyte composition of ECG:fluid balance, electrolyte balance, and acid-base balance.balance, and acid-base balance.

Seletive PermeabilityExcitabilityConductivityAutomaticity

BIOPOTENTIALSBIOPOTENTIALS

Cell-Membrane Resting PotentialCell-Membrane Resting Potential

+-

needle electrode

membrane

reference electrode outside of cell

Advance needle electrode across the cell membrane….

BIOPOTENTIALSBIOPOTENTIALS

Cell-Membrane Resting PotentialCell-Membrane Resting Potential

+-

0 mV

….a “resting” potential of -90 mV is observed inside the cell with respect to outside the cell

Advance needle electrode across the cell membrane….

Cell-Membrane Resting PotentialCell-Membrane Resting Potential

+

The resting potential is maintained by an ATP powered sodium-potassium “pump” within the membrane that transports Na+ ions outward and K+ ions inward (3 Na+ per 2 K+).

Na+

K+ Na+

Na+

The gradient of ion-concentration separates charge across the membrane with an equal and opposite electrical gradient of -90 mV.

-

K+

Advance needle electrode across the cell membrane….

-

--- -- ---

---

----

----

---

-

-- -

+ +++

+++++++

+++++++

++++

+ +

Cell Membrane Action Potential (AP)Cell Membrane Action Potential (AP)

+-

Stimulate the cell….

0 mV

….a transmembrane “AP” is observed with 5 characteristic phases (Φ)

Cell Membrane Action Potential (AP)Cell Membrane Action Potential (AP)

+-

Stimulate the cell….

Φ0 – Upstroke

Φ2 – Plateau (absolute

refractory)Φ3 – Recovery

(relative refractory)

Φ4 – Resting

Φ1 – Initial Recovery

0 mV

Cell Membrane Ion ChannelsCell Membrane Ion ChannelsVoltage-gated, ion-selective channels open and close to generate the AP

Many types of channels are known, each selective to a specific species of Na+, K+, and Ca++ ions

Cell Membrane Ion ChannelsCell Membrane Ion ChannelsVoltage-gated, ion-selective channels open and close to generate the AP

….with 4 “phases” of protein groups (I-IV)….

….including 1 “P-loop” polypeptide chain

….and 6 “sub-groups” within each phase….

All channels have a common structure that spans the membrane….

inside outsidemembrane

Cell Membrane Ion ChannelsCell Membrane Ion ChannelsVoltage-gated, ion-selective channels open and close to generate the AP NH2

COOH

“unroll” channel....

Cell Membrane Ion ChannelsCell Membrane Ion ChannelsFlattened view presents clearer view of the channel structure NH2

COOH

membrane (phospholipid bilayer)

amino-end

carboxy-end

IN OUT

IN OUT

Cell Membrane Ion ChannelsCell Membrane Ion Channels

NH2

COOH

….are repeated, forming each of the

4 phases (I-IV)

subgroups S1-S6….

Flattened view presents clearer view of the channel structure

IN OUT

IN OUT

Cell Membrane Ion ChannelsCell Membrane Ion Channels

NH2

COOH

“P-loops” form the narrowest part of

the channel responsible for gating ion-flow

Flattened view presents clearer view of the channel structure

IN OUT

IN OUT

Cell Membrane Ion ChannelsCell Membrane Ion ChannelsFunctional and structural evidence suggests that P-loops are central to…. NH2

COOH

• sensing voltage• filtering ion species• mechanical actuation

S6

S5

Cell Membrane Ion ChannelsCell Membrane Ion Channels

S6

S5

Functional and structural evidence suggests that P-loops are central to actuation

• P-loops extend (or twist) for channel activation

Cell Membrane Ion ChannelsCell Membrane Ion Channels

S6

S5

Functional and structural evidence suggests that P-loops are central to actuation

• P-loops retract (or twist) for channel inactivation

Na+

Cell Membrane Ion ChannelsCell Membrane Ion ChannelsTransmembrane AP formation follows an organized sequence in response to stimulation:

Φ0 – Upstroke

1) Fast, inward Na+ channels open, rapidly depolarizing the membrane and triggering closure of the channels (Φ0 – upstroke and overshoot)

K+

Na+

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ1 – Initial Recovery

Transmembrane AP formation follows an organized sequence in response to stimulation:

2) Slower, outward K+ channels sense the rising voltage and open, diminishing the overshoot (Φ1 – Initial Recovery)

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ2 – Plateau (absolute refractory)

K+

Ca++

Transmembrane AP formation follows an organized sequence in response to stimulation:

3) Slower, inward Ca++ channels open, matching outward K+ and maintaining the membrane near 0 mV (Φ2 – Plateau)

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ3 – Recovery (relative refractory)

K+

K+

Transmembrane AP formation follows an organized sequence in response to stimulation:

4) K+ conduction increases and Ca++ decreases, repolarizing the membrane (Φ3 – Recovery)

Ca++

Cell Membrane Ion ChannelsCell Membrane Ion ChannelsTransmembrane AP formation follows an organized sequence in response to stimulation:

5) Na+– K+ pump helps converge and maintain resting potential near -90 mV (Φ4 – Resting)

Φ4 – Resting

Na+

K+ Na+

Na+

K+

ElectrophysiologyElectrophysiology

cell membrane

K+

Na+ Na +Ca++ K+

ATPase

0

12

3

4

ARP

ERP

RRP

Diastole

Actin filamentMyosin

Excitability Automatism

conduction

Potassium (KPotassium (K++)) 3500 mmol3500 mmol– Major ICF cationMajor ICF cation

intracellular 120-125 mEq/literintracellular 120-125 mEq/liter plasma 3.8-5.0 mEq/literplasma 3.8-5.0 mEq/liter

– Very importantVery important role in resting membrane role in resting membrane potential (RMP) and in action potentialspotential (RMP) and in action potentials

– Regulation:Regulation: Direct Effect: excretion by kidney tubule Direct Effect: excretion by kidney tubule AldosteroneAldosterone

[[KK++]]pp (n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

[[KK++]]pp (n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Dosaggio KDosaggio K++ inadeguato a valutazione del K inadeguato a valutazione del K++ totale totale Riduzione con l’età del contenuto corporeo di K+

(riduzione massa muscolare magra (75% K+ LIC)

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Ridotto apporto in malattie acute o malnutrizione Nausea o Vomito (perdite per via extra-renale)

-- FEKFEK++ <25-30mEq/24 <25-30mEq/24 Tereapie Diuretiche con tiazidici o diuretici dell’ansa

(20% pts Ipo-K+ dose dipendente) - FEKFEK++ > 25-30 mEq/24 ore > 25-30 mEq/24 ore

Stati di Alcalosi Metabolica (iperaldosteronismo)

Infusione di penicilline iv ad alte dosi:Infusione di penicilline iv ad alte dosi:• Carbenecillina (dose tra 26 e 36 grammi Carbenecillina (dose tra 26 e 36 grammi

ciascun grammo contenente 4.7 mEq di ciascun grammo contenente 4.7 mEq di NaNa+ + ).).AmfotericinaAmfotericinaDeficit di MgDeficit di Mg++++ PoliuriaPoliuriaEccessiva sudorazioneEccessiva sudorazione

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

K+

Na+

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ1 – Initial Recovery

Transmembrane AP formation follows an organized sequence in response to stimulation:

2) Slower, outward K+ channels sense the rising voltage and open, diminishing the overshoot (Φ1 – Initial Recovery)

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ2 – Plateau (absolute refractory)

K+

Ca++

Transmembrane AP formation follows an organized sequence in response to stimulation:

3) Slower, inward Ca++ channels open, matching outward K+ and maintaining the membrane near 0 mV (Φ2 – Plateau)

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ3 – Recovery (relative refractory)

K+

K+

4) K+ conduction increases and Ca++ decreases, repolarizing the membrane (Φ3 – Recovery)

Ca++

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Cardiac ArrhythmiasCardiac Arrhythmias• Synus BradicardiaSynus Bradicardia• Ectopic Atriale and/or Ventricular Activity Ectopic Atriale and/or Ventricular Activity • SVST, VST SVST, VST • Complete AV block, VF Complete AV block, VF

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

channelwrap-around

Cardiac ArrhythmiasCardiac Arrhythmias• Synus BradicardiaSynus Bradicardia• Ectopic Atriale and/or Ectopic Atriale and/or

Ventricular Activity Ventricular Activity • SVST, VST SVST, VST • Complete AV block, VF Complete AV block, VF

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

channelwrap-around

Cardiac ArrhythmiasCardiac Arrhythmias• Synus BradicardiaSynus Bradicardia• Ectopic Atriale and/or Ectopic Atriale and/or

Ventricular Activity Ventricular Activity • SVST, VST SVST, VST • Complete AV block, VF Complete AV block, VF

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

channelwrap-around

Cardiac ArrhythmiasCardiac Arrhythmias• Synus BradicardiaSynus Bradicardia• Ectopic Atriale and/or Ectopic Atriale and/or

Ventricular Activity Ventricular Activity • SVST, VST SVST, VST • Complete AV block, VF Complete AV block, VF

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

channelwrap-around

Cardiac ArrhythmiasCardiac Arrhythmias• Synus BradicardiaSynus Bradicardia• Ectopic Atriale and/or Ectopic Atriale and/or

Ventricular Activity Ventricular Activity • SVST, VST SVST, VST • Complete AV block, VF Complete AV block, VF

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Cardiac ArrhythmiasCardiac Arrhythmias• Synus BradicardiaSynus Bradicardia• Ectopic Atriale and/or Ectopic Atriale and/or

Ventricular Activity Ventricular Activity • SVST, VST SVST, VST • Complete AV block, VF Complete AV block, VF

channelwrap-around

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Cardiac ArrhythmiasCardiac Arrhythmias• Synus BradicardiaSynus Bradicardia• Ectopic Atriale and/or Ectopic Atriale and/or

Ventricular Activity Ventricular Activity • SVST, VST SVST, VST • Complete AV block, VF Complete AV block, VF

channelwrap-around

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Cardiac ArrhythmiasCardiac Arrhythmias• Synus BradicardiaSynus Bradicardia• Ectopic Atriale and/or Ectopic Atriale and/or

Ventricular Activity Ventricular Activity • SVST, VST SVST, VST • Complete AV block, VF Complete AV block, VF

channelwrap-around

1.1. Correlare [KCorrelare [K++]]p p a pH a pH

E’ più grave una Kaliemia bassa e pH N o basso, rispetto alla E’ più grave una Kaliemia bassa e pH N o basso, rispetto alla stessa kaliemia con un pH alcalino stessa kaliemia con un pH alcalino E’ corretto dare KCl in tutte le forme di IPO-K con alcalosi E’ corretto dare KCl in tutte le forme di IPO-K con alcalosi metabolicametabolica

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

2.2. Calcolo deficit teorico [KCalcolo deficit teorico [K++]]pp

ΔΔ (4,5-[K]p) x 0,6 x 0,6 x PC(4,5-[K]p) x 0,6 x 0,6 x PC50% /1-2 h (EKG monitoring) 50% /1-2 h (EKG monitoring)

3.3. Spesso riduzione [MgSpesso riduzione [Mg++++]]pp

associazione Mgassociazione Mg22SoSo44 (1-2 gr = 8-16 mEq di Mg in 2-4 ore) (1-2 gr = 8-16 mEq di Mg in 2-4 ore) tranne se marcata ipotensione o tachiaritmie tranne se marcata ipotensione o tachiaritmie

TERAPIA PER EV (diluire in fisiologica)

K+ compresa tra 2,5-3 mEq/L (20 mEq/100 ml; v max 10mEq/h)

[[KK++]]pp < 3,5 mm/L < 3,5 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Nel DKA correggere prima il deficit di K+ e poi l’acidosi

K+ <2,5 mEq/L e segni ECG importanti (40 mEq di K+; v max 20-30 mEq/h) monitoraggio ECG (monitorare ogni 2-4 h la [K])

fino a 40-60 mEq/h in vena centrale e sotto guida ECG

K+

Na+

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ1 – Initial Recovery

Transmembrane AP formation follows an organized sequence in response to stimulation:

2) Slower, outward K+ channels sense the rising voltage and open, diminishing the overshoot (Φ1 – Initial Recovery)

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ2 – Plateau (absolute refractory)

K+

Ca++

Transmembrane AP formation follows an organized sequence in response to stimulation:

3) Slower, inward Ca++ channels open, matching outward K+ and maintaining the membrane near 0 mV (Φ2 – Plateau)

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ3 – Recovery (relative refractory)

K+

K+

Transmembrane AP formation follows an organized sequence in response to stimulation:

4) K+ conduction increases and Ca++ decreases, repolarizing the membrane (Φ3 – Recovery)

Ca++

[[KK++]]pp > 5,0 mm/L > 5,0 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Φ3 – Recovery (relative refractory)

K+

K+

Ca++

[[KK++]]pp > 5,0 mm/L > 5,0 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

[[KK++]]pp > 5,0 mm/L > 5,0 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Action Potential assessmentAction Potential assessment– Six stages Six stages

Resting potential less electronegative Resting potential less electronegative Reduction Reduction ΔΔ resting/soglia (mV) resting/soglia (mV) Reduction over-shooting Reduction over-shooting

Increase uprightIncrease upright Impulse conduction slowerImpulse conduction slower Increase gK Increase gK

Decreased excretionDecreased excretion– DrugsDrugs, renal failure, hypoaldosteronism, renal failure, hypoaldosteronism

Increased productionIncreased production– Trauma, tumor lysisTrauma, tumor lysis

Volume contractionVolume contraction Intense fisical stressIntense fisical stress Insulin deficitInsulin deficit Digoxin toxicityDigoxin toxicity Miorilassanti depolarizzanti Miorilassanti depolarizzanti

(Succinilcolina)(Succinilcolina) Hypertonic statesHypertonic states AcidosisAcidosis (shift H+/K+)

[[KK++]]pp > 5,0 mm/L > 5,0 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

EKG assessmentEKG assessment

[[KK++]]pp > 5,0 mm/L > 5,0 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

– Four stages of EKG changesFour stages of EKG changes Peaked T wavesPeaked T waves PR prolongationPR prolongation QRS wideningQRS widening Sine waves Sine waves

– The “fifth” and final stage if hyperkalemia The “fifth” and final stage if hyperkalemia is not addressed…is not addressed… PEA or asystole (yikes!!!)PEA or asystole (yikes!!!)

Hyperkalemia:Hyperkalemia:TreatmentTreatment

Loop DiureticsLoop Diuretics KayexalateKayexalate

(50 gr Kajexhalate (50 gr Kajexhalate riduzione Kriduzione K++ 0,5 mEq/l) 0,5 mEq/l) NNaaHCOHCO33 60-100 mEq/30’-60’ 60-100 mEq/30’-60’ (consente di guadagnare fino a 6-8 ore, (consente di guadagnare fino a 6-8 ore, ripetibile, ma attenzione al sovraccarico di Naripetibile, ma attenzione al sovraccarico di Na++) )

Insulin/D50 Insulin/D50 Albuterol Nebs Albuterol Nebs Calcium Gluconate or ClorureCalcium Gluconate or Clorure

Emergency or non-emergency Rx Emergency or non-emergency Rx (usually takes 4-6 hours to work)(usually takes 4-6 hours to work)

[[KK++]]pp > 5,0 mm/L > 5,0 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

– Direct elimination of KDirect elimination of K++ from body from body– Sodium polystyrene sufonate (KSodium polystyrene sufonate (K++ binding resin) plus binding resin) plus

sorbitolsorbitol Give Kayexalate 30-60 gmGive Kayexalate 30-60 gm

– PO if patient can toleratePO if patient can tolerate– PR (retention enema) if upper GI problemsPR (retention enema) if upper GI problems– Patient needs to have a colon for this to work! Patient needs to have a colon for this to work!

– Hemodialysis as last resort or in severe Hemodialysis as last resort or in severe cases cases

Emergency RxEmergency Rx– Part A: Shift KPart A: Shift K++ into cells into cells

Will buy you 1-4 hours before direct Will buy you 1-4 hours before direct elimination methods “kick-in”elimination methods “kick-in”

Insulin/dextrose therapyInsulin/dextrose therapy– Give 10U regular insulin IV push, together with 1 Give 10U regular insulin IV push, together with 1

ampule (50mL) D50 IV pushampule (50mL) D50 IV push Adjuncts (usually not necessary)Adjuncts (usually not necessary)

– Albuterol nebulizer (continuous neb)Albuterol nebulizer (continuous neb)– Sodium bicarbonate 1 ampule IV pushSodium bicarbonate 1 ampule IV push– Lasix: yes or no? Lasix: yes or no? USE WITH CAUTIONUSE WITH CAUTION

Beware rebound hyperkalemia!!!Beware rebound hyperkalemia!!!

[[KK++]]pp > 5,0 mm/L > 5,0 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Emergency RxEmergency Rx– Part B: oppose toxic effects on cell membranePart B: oppose toxic effects on cell membrane

IV calcium infusion (gluconate preferred over chloride)IV calcium infusion (gluconate preferred over chloride)– Less toxic effects if IV extravasationLess toxic effects if IV extravasation

Give 1-2, 10mL ampules of 10% Calcium gluconate over 2-5 Give 1-2, 10mL ampules of 10% Calcium gluconate over 2-5 minutesminutes

– Too fast—pukey pukey!!!Too fast—pukey pukey!!! Keep EKG machine attached to patient!!!Keep EKG machine attached to patient!!!

– EKG changes will diminish in 1-3 minutesEKG changes will diminish in 1-3 minutes

[[KK++]]pp > 5,0 mm/L > 5,0 mm/L(n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

Nernst: R x T logn [K]iz x F [K]e

CALCIOCALCIOCalcio corporeo tot

1-2 kg (20.000-50.000 mmol)

99% nelle ossa 1% nei liquidi

ECF 0,1% ICF 0,9%

0,03% plasma 0,07 liq interstiziale

50% ionizzato 40% legato a proteine 10% chelato

Ca sierico v.n. 2,1-2,6 mmol/lCa ionizzato v.n. 1,1-1,3 mmol/lQUOTA ATTIVA

Calcitonin Calcitonin and Estrogenand Estrogen Calcium

CalciumParathormoneParathormone Ca++ reabsorbing from Ca++ reabsorbing from

the bone back into the the bone back into the blood,blood,

Stimulate renal Stimulate renal reabsorbing of Ca++ reabsorbing of Ca++

Stimulate renal Stimulate renal conversion of conversion of Vit D2 Vit D2 Vit D3c Vit D3c

Stimulate Calcium Stimulate Calcium deposition in the bonesdeposition in the bones

Approach to CalcemiaApproach to Calcemia

Frazione ionizzata quella Frazione ionizzata quella ATTIVAATTIVA Frazione ionizzata misurata Frazione ionizzata misurata DIRETTAMENTE DIRETTAMENTE

(tentativi di calcolo su pH e proteinemia (tentativi di calcolo su pH e proteinemia imprecisi) imprecisi) Scambi Scambi LIC/LEC e LIC/LICLIC/LEC e LIC/LIC (Met. ICF citosol/organelli in condizioni di (Met. ICF citosol/organelli in condizioni di ipossia/ischemia) ipossia/ischemia)

Comportamento reciproco Comportamento reciproco Ca e P Ca e P (se prodotto >60 mg/dl (se prodotto >60 mg/dl Sali che Sali che precipitano)precipitano)

K+

Na+

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ1 – Initial Recovery

Transmembrane AP formation follows an organized sequence in response to stimulation:

2) Slower, outward K+ channels sense the rising voltage and open, diminishing the overshoot (Φ1 – Initial Recovery)

Cell Membrane Ion ChannelsCell Membrane Ion Channels

Φ2 – Plateau (absolute refractory)

K+

Ca++

Transmembrane AP formation follows an organized sequence in response to stimulation:

3) Slower, inward Ca++ channels open, matching outward K+ and maintaining the membrane near 0 mV (Φ2 – Plateau)

Chelazione:Chelazione: pancreatitis, Alcalosis (pancreatitis, Alcalosis (pH > 0,1 unit [ Ca ionized] reduction 0,1 mmol/L), Citrate-intoxication , Citrate-intoxication

Ipoparatiroidismo:Ipoparatiroidismo: sepsis, burns, interventi sulle paratiroidi sepsis, burns, interventi sulle paratiroidi

Ipovitaminosi D:Ipovitaminosi D: apporto inadeguato, malassorbimento, Insuff. Renale, apporto inadeguato, malassorbimento, Insuff. Renale, Epatopatie Epatopatie Riduzione Turn-over osseo:Riduzione Turn-over osseo: osteoporosi, invecchiamento osteoporosi, invecchiamento

Drugs: Drugs: EDTA, fenitoina, protamina, gentamicinaEDTA, fenitoina, protamina, gentamicina

Approach to CalcemiaApproach to Calcemia

HypocalcemiaHypocalcemiaSymptomsSymptoms Neuromuscular irritabilityNeuromuscular irritability Chvostek’s/Trousseau’sChvostek’s/Trousseau’s Laryngo/broncospasm, Laryngo/broncospasm, Apnea syndromeApnea syndrome Diarrhea (increased peristalsisDiarrhea (increased peristalsis Arrhythmias and hypotensionArrhythmias and hypotension Prolonged QTcProlonged QTc

(prolonged plateau)(prolonged plateau) T wave inversion T wave inversion Prolonged conduction Prolonged conduction

(AV block, (AV block, AVNRT)AVNRT)

AIRWAYS SUPPORT AIRWAYS SUPPORT Gluconate-Ca++ 10 ml:Gluconate-Ca++ 10 ml: 93 mg (2,3 mmol)93 mg (2,3 mmol)CaCl2 10 ml:CaCl2 10 ml: 272 mg (6,8 mmol)272 mg (6,8 mmol)My approach:My approach: 200 mg 200 mg (CaCl2 5,5ml/Glu-Ca++ 22 ml)(CaCl2 5,5ml/Glu-Ca++ 22 ml)

+ 1-2 mg/Kg/h+ 1-2 mg/Kg/h

Absolutely indication for Ca++ administrationSymptomatic IpoCalcemiaInonized Ca++ < 0,8 mmol/L

Overdosage of Ca++ Channel blocked

Acute symptomatic Acute symptomatic hypocalcemia treatmenthypocalcemia treatment

Hypomagnesemia OverviewHypomagnesemia Overview Most of total body MgMost of total body Mg++++ is ICF is ICF

– Serum levels may Serum levels may NOTNOT reflect intracellular status reflect intracellular status– Intracellular magnesium depletion has been shown to Intracellular magnesium depletion has been shown to

occur in the setting of decreased, normal, and elevated occur in the setting of decreased, normal, and elevated serum magnesium levelsserum magnesium levels

– If pH increase, improve the legam between Mg and If pH increase, improve the legam between Mg and serum proteins, then reduce ionized quoteserum proteins, then reduce ionized quote

Highest risk pts for MgHighest risk pts for Mg++++ (Alcoholics, critically ill pts, refeeding syndrome (Alcoholics, critically ill pts, refeeding syndrome pts) pts)

Most pts are asymptomaticMost pts are asymptomatic

Rare symptoms:Rare symptoms: -- usually neurologic, muscular, cardiac usually neurologic, muscular, cardiac

Common causes of Hypo-MgCommon causes of Hypo-Mg++++

Malabsorptive syndromesMalabsorptive syndromes Alcohol ingestion (renal losses)Alcohol ingestion (renal losses) Thiazide/loop diuretic administrationThiazide/loop diuretic administration Amphotericin administrationAmphotericin administration Acute/chronic diarrheaAcute/chronic diarrhea DKADKA Refeeding syndromeRefeeding syndrome Inadequate TPN dosingInadequate TPN dosing

HYPOMAGNESEMIAHYPOMAGNESEMIA

Φ4 – Resting

Na+

K+ Na+

Na+

K+

Quota misurabile minima (max ICF)Quota misurabile minima (max ICF) Quota IONIZZATA biologicamente attiva Quota IONIZZATA biologicamente attiva

(50-60% della quota plasmatica)(50-60% della quota plasmatica) Se pH aumenta, legame proteico aumenta e quota Se pH aumenta, legame proteico aumenta e quota

ionizzata si riduce (come Caionizzata si riduce (come Ca++++)) Ipo-MgIpo-Mg++++ anche se conc. Plasmatica totale normale anche se conc. Plasmatica totale normale

Unlike KUnlike K++ replacement, Mg replacement, Mg++++ replacement replacement (usually) involves IV replacement(usually) involves IV replacement– All PO magnesium salts are all poorly absorbedAll PO magnesium salts are all poorly absorbed– High doses of PO magnesium usually leads to diarrheaHigh doses of PO magnesium usually leads to diarrhea

Conversion rule: 8 mEq of Mg2SO4 equals 1 gram of Conversion rule: 8 mEq of Mg2SO4 equals 1 gram of Mg2SO4 (HVA CPRS)Mg2SO4 (HVA CPRS)

– 1.6-2.0 mg/dL1.6-2.0 mg/dL Give 2-4 gram IVPB (16-32 mEq) at 1 gr/hourGive 2-4 gram IVPB (16-32 mEq) at 1 gr/hour

– 1.0-1.6 mg/dL1.0-1.6 mg/dL Give 4-8 gram IVPB (32-64 mEq) Give 4-8 gram IVPB (32-64 mEq)

– <1.0 mg/dL<1.0 mg/dL Can give up to 8-12 gram IVPB (64-96 mEq) Can give up to 8-12 gram IVPB (64-96 mEq)

Approach to Hypo-Mg++Approach to Hypo-Mg++

Housekeeping/follow upHousekeeping/follow up– BE GENTLEBE GENTLE in patients with acute or chronic in patients with acute or chronic

renal failurerenal failure May wish to cut doses in half, double intervals, May wish to cut doses in half, double intervals,

or not replace at allor not replace at all May need to monitor very closelyMay need to monitor very closely

Approach to Hypo-MgApproach to Hypo-Mg++++

– BE AGGRESSIVEBE AGGRESSIVE in DKA patients, IV diuresis in DKA patients, IV diuresis

patients, and alcoholicspatients, and alcoholics May want to keep magnesium over 2.0 or even May want to keep magnesium over 2.0 or even

2.5 mg/dL in cardiac patients, especially in 2.5 mg/dL in cardiac patients, especially in those with arrhythmiasthose with arrhythmias

ElectrolytesElectrolytes

Phosphate (HPhosphate (H22POPO44--, HPO, HPO44

2-2-, PO, PO443-3-))

– Important ICF anions; plasma 1.7-2.6 mEq/literImportant ICF anions; plasma 1.7-2.6 mEq/liter most (85%) is stored in bone as calcium saltsmost (85%) is stored in bone as calcium salts also combined with lipids, proteins, carbohydrates, nucleic acids also combined with lipids, proteins, carbohydrates, nucleic acids

(DNA and RNA), and high energy phosphate transport (DNA and RNA), and high energy phosphate transport compoundcompound

important acid-base buffer in body fluidsimportant acid-base buffer in body fluids

– Regulation - regulated in an inverse relationship with Regulation - regulated in an inverse relationship with CaCa2+2+ by PTH and Calcitonin by PTH and Calcitonin

– Homeostatic imbalancesHomeostatic imbalances Phosphate concentrations shift oppositely from calcium Phosphate concentrations shift oppositely from calcium

concentrations and symptoms are usually due to the related concentrations and symptoms are usually due to the related calcium excess or deficitcalcium excess or deficit

Causes of HypophosphatemiaCauses of Hypophosphatemia

Refeeding syndromeRefeeding syndrome DKADKA Vitamin D deficiencyVitamin D deficiency Malabsorptive syndromesMalabsorptive syndromes AlcoholismAlcoholism Inadequate TPN dosingInadequate TPN dosing

Approach to HypophosphatemiaApproach to Hypophosphatemia Rx in hospitalized patientsRx in hospitalized patients

– Mild to moderate hypophosphatemiaMild to moderate hypophosphatemia 1.5 -2.4 mg/dL1.5 -2.4 mg/dL Give phosphorus in the form of KGive phosphorus in the form of K++ or Na or Na++ salts PO BID to salts PO BID to

TID as neededTID as needed– Usually given as 1-2 packets of “neutraphos” BID to TIDUsually given as 1-2 packets of “neutraphos” BID to TID

– Severe deficiencySevere deficiency <1.5 mg/dL<1.5 mg/dL Give IVPB in the form of sodium or potassium phosphateGive IVPB in the form of sodium or potassium phosphate

– Usually given as 20-40 mEq/mmol rider infused over 2-4 hoursUsually given as 20-40 mEq/mmol rider infused over 2-4 hours

– Reasess labs QD to TID as neededReasess labs QD to TID as needed

Grazie per la Grazie per la CORTESE CORTESE ATTENZIONEATTENZIONE