2009 terni, workshop interattivo, elettroliti e cuore

1. Elettroliti e CUOREElettroliti e CUORE
Stefano Nardi, MD, PhDStefano Nardi, MD, PhD
AZIENDA OSPEDALIERA SANTA MARIA, TERNIAZIENDA OSPEDALIERA SANTA MARIA, TERNI
DIPARTIMENTO CARDIOTORACOVASCOLAREDIPARTIMENTO CARDIOTORACOVASCOLARE
STRUTTURA COMPLESSA DI CARDIOLOGIASTRUTTURA COMPLESSA DI CARDIOLOGIA
CENTRO DI ARITMOLOGIA CLINICA EDCENTRO DI ARITMOLOGIA CLINICA ED
ELETTROFISIOLOGIA CARDIACAELETTROFISIOLOGIA CARDIACA
LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONELABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE

2. .....chiara.........chiara....
Parlare di tutto.......
......in maniera approfondita,
...ed in poco tempo!!!!

3. Missione impossibileMissione impossibile

4. HH22O & Electrolytes distributionO & Electrolytes distribution
 Non-electrolytesNon-electrolytes
– formed by only covalent bondsformed by only covalent bonds
– do not form charged ions in solutiondo not form charged ions in solution
 ElectrolytesElectrolytes
– formed with some ionic bonds;formed with some ionic bonds;
– Dissociate into (+) & (-) inDissociate into (+) & (-) in
solutionssolutions (acids, bases, salts)(acids, bases, salts)
– 4 important physiological4 important physiological
functions in the bodyfunctions in the body
 essential minerals in certainessential minerals in certain
biochemical reactionsbiochemical reactions
 CTR Posm = CTR movement ofCTR Posm = CTR movement of
water between compartmentswater between compartments
 maintain acid-base balancemaintain acid-base balance
 conduct electrical currentsconduct electrical currents
(depolarization events)(depolarization events)

5. Some Electrolyte ReferenceSome 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

6. 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 electrostatichelps balance osmotic potential and electrostatic
equilibrium between fluid compartmentsequilibrium between fluid compartments
 plasma membranes tend to be leaky to Clplasma membranes tend to be leaky to Cl--
anionsanions
– Regulation: aldosteroneRegulation: aldosterone
K+
K+
K+
K+
_
_ _
_
_
Na+
Na+
Na+
Na+
Cl-
Cl-
Cl-
Cl-
Cl-
Cl-

7.  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/literplasma 4.6-5.5 mEq/liter
 most stored in bone (98%)most stored in bone (98%)
 Magnesium (MgMagnesium (Mg2+2+
))
– 22ndnd
most abundant ICF cationmost abundant ICF cation
 1.3-2.1 mEq/liter in plasma1.3-2.1 mEq/liter in plasma
 more than half stored in bone,more than half stored in bone,
most of the rest in ICFmost of the rest in ICF
Electrolytes (ICF)Electrolytes (ICF)

8. 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 tubuleDirect Effect: excretion by kidney tubule
 AldosteroneAldosterone
 Calcium (CaCalcium (Ca2+2+
))
– Regulation:Regulation:
 Parathyroid Hormone (PTH) -Parathyroid Hormone (PTH) - ↑↑ blood Cablood Ca2+2+
 Calcitonin (CT) -Calcitonin (CT) - ↓↓ blood Cablood 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, andnerve transmission in CNS, and myocardial functioningmyocardial functioning

9. 0.9%
NaCl
3% NaCl
0.9%
NaCl
0.5% NaCl
Hypotonic vs HypertonicHypotonic vs Hypertonic

10. Water and Electrolyte balanceWater and Electrolyte balance
IPERTONICITÀ IPOTONICITÀ
Osmocettori ipotalamici
attivati
Osmocettori ipotalamici
inibiti
↑sete ↓sete
↑ Liberazione
ADH
↓ Liberazione
ADH
↑ Apporto idrico ↓ Apporto idrico
Diuresi contratta Diuresi aumentata
(2x[Na+
] ) + BUN(mg/dl) + glucosio(mg/dl)
2,8 18

11. Electrolyte BalanceElectrolyte Balance

12.  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

13. 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)

14. Rhythm Basics OverviewRhythm Basics Overview
 Electrolytes can affect theElectrolytes can affect the
Conduction SystemConduction System
– Cardiac FunctionCardiac Function
– Action PotentialAction Potential
– Impulse FormationImpulse Formation
– Impulse ConductionImpulse Conduction
 Three types of homeostasis are involved in theThree types of homeostasis are involved in the
maintenance of normal volume and normalmaintenance of normal volume and normal
composition of ECG:fluid balance, electrolytecomposition of ECG:fluid balance, electrolyte
balance, and acid-base balance.balance, and acid-base balance.

15. Seletive Permeability
Excitability
Conductivity
Automaticity
BIOPOTENTIALSBIOPOTENTIALS

16. Cell-Membrane Resting PotentialCell-Membrane Resting Potential
+
-
needle
electrode
membrane
reference
electrode outside
of cell
Advance needle electrode
across the cell membrane….
BIOPOTENTIALSBIOPOTENTIALS

17. 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….

18. 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….
-
-
-- --
---
--
-
-
---
-
---
--
-
-
-- -
+
+
+
+
+++
+
+
+
+
+++
+
+
+
+
+
+
+
+
+
+

19. 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)

20. 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

21. Cell Membrane Ion ChannelsCell Membrane Ion Channels
Voltage-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

22. Cell Membrane Ion ChannelsCell Membrane Ion Channels
Voltage-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

23. Cell Membrane Ion ChannelsCell Membrane Ion Channels
Voltage-gated, ion-selective channels
open and close to generate the AP NH2
COOH
“unroll” channel....

24. Cell Membrane Ion ChannelsCell Membrane Ion Channels
Flattened view presents clearer
view of the channel structure NH2
COOH
membrane
(phospholipid bilayer)
amino-end
carboxy-end
IN OUT
IN OUT

25. 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

26. 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

27. Cell Membrane Ion ChannelsCell Membrane Ion Channels
Functional and structural evidence
suggests that P-loops are central to…. NH2
COOH
• sensing voltage
• filtering ion species
• mechanical actuation
S6
S5

28. 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

29. 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

30. Na+
Cell Membrane Ion ChannelsCell Membrane Ion Channels
Transmembrane 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)

31. 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)

32. 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)

33. 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++

34. Cell Membrane Ion ChannelsCell Membrane Ion Channels
Transmembrane 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+

35. ElectrophysiologyElectrophysiology
cell membrane
K+
Na+ Na +
Ca++
K+
ATP
ase
0
1
2
3
4
ARP
ERP
RRP
Diastole
Actin filamentMyosin
Excitability Automatism
conduction

36.  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 membranerole in resting membrane
potential (RMP) and in action potentialspotential (RMP) and in action potentials
– Regulation:Regulation:
 Direct Effect: excretion by kidney tubuleDirect Effect: excretion by kidney tubule
 AldosteroneAldosterone
[[KK++
]]pp (n.v. 3.5-5.0 mm/l)(n.v. 3.5-5.0 mm/l)

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

38.  Dosaggio KDosaggio K++
inadeguato a valutazione del Kinadeguato a valutazione del K++
totaletotale
 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)

39. Infusione di penicilline iv ad alte dosi:Infusione di penicilline iv ad alte dosi:
• Carbenecillina (dose tra 26 e 36 grammiCarbenecillina (dose tra 26 e 36 grammi
ciascun grammo contenente 4.7 mEq diciascun grammo contenente 4.7 mEq di NaNa++
).).
AmfotericinaAmfotericina
Deficit di MgDeficit di Mg++++
PoliuriaPoliuria
Eccessiva 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)

40. 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)

41. 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)

42. 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++

43. [[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)

44. Cardiac ArrhythmiasCardiac Arrhythmias
• Synus BradicardiaSynus Bradicardia
• Ectopic Atriale and/or Ventricular ActivityEctopic Atriale and/or Ventricular Activity
• SVST, VSTSVST, VST
• Complete AV block, VFComplete 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)

45. channel
wrap-
around
Cardiac ArrhythmiasCardiac Arrhythmias
• Synus BradicardiaSynus Bradicardia
• Ectopic Atriale and/orEctopic Atriale and/or
Ventricular ActivityVentricular Activity
• SVST, VSTSVST, VST
• Complete AV block, VFComplete 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)

46. channel
wrap-
around
Cardiac ArrhythmiasCardiac Arrhythmias
• Synus BradicardiaSynus Bradicardia
• Ectopic Atriale and/orEctopic Atriale and/or
Ventricular ActivityVentricular Activity
• SVST, VSTSVST, VST
• Complete AV block, VFComplete 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)

47. channel
wrap-
around
Cardiac ArrhythmiasCardiac Arrhythmias
• Synus BradicardiaSynus Bradicardia
• Ectopic Atriale and/orEctopic Atriale and/or
Ventricular ActivityVentricular Activity
• SVST, VSTSVST, VST
• Complete AV block, VFComplete 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)

48. channel
wrap-
around
Cardiac ArrhythmiasCardiac Arrhythmias
• Synus BradicardiaSynus Bradicardia
• Ectopic Atriale and/orEctopic Atriale and/or
Ventricular ActivityVentricular Activity
• SVST, VSTSVST, VST
• Complete AV block, VFComplete 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)

49. [[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/orEctopic Atriale and/or
Ventricular ActivityVentricular Activity
• SVST, VSTSVST, VST
• Complete AV block, VFComplete AV block, VF
channel
wrap-
around

50. [[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/orEctopic Atriale and/or
Ventricular ActivityVentricular Activity
• SVST, VSTSVST, VST
• Complete AV block, VFComplete AV block, VF
channel
wrap-
around

51. [[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/orEctopic Atriale and/or
Ventricular ActivityVentricular Activity
• SVST, VSTSVST, VST
• Complete AV block, VFComplete AV block, VF
channel
wrap-
around

52. 1.1. Correlare [KCorrelare [K++
]]pp a pHa pH
E’ più grave una Kaliemia bassa e pH N o basso, rispetto allaE’ più grave una Kaliemia bassa e pH N o basso, rispetto alla
stessa kaliemia con un pH alcalinostessa kaliemia con un pH alcalino
E’ corretto dare KCl in tutte le forme di IPO-K con alcalosiE’ 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 PC
50% /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 tachiaritmietranne se marcata ipotensione o tachiaritmie

53. 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

54. 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)

55. 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)

56. 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++

57. [[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++

58. [[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)

59. [[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 stagesSix stages
 Resting potential less electronegativeResting potential less electronegative
 ReductionReduction ΔΔ resting/soglia (mV)resting/soglia (mV)
 Reduction over-shootingReduction over-shooting
 Increase uprightIncrease upright
 Impulse conduction slowerImpulse conduction slower
 Increase gKIncrease gK

60.  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 depolarizzantiMiorilassanti 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)

61.  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 wavesSine waves
– The “fifth” and final stage if hyperkalemiaThe “fifth” and final stage if hyperkalemia
is not addressed…is not addressed…
 PEA or asystole (yikes!!!)PEA or asystole (yikes!!!)

62. 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/D50Insulin/D50
 Albuterol NebsAlbuterol Nebs
 Calcium Gluconate or ClorureCalcium Gluconate or Clorure

63.  Emergency or non-emergency RxEmergency 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 bodyfrom body
– Sodium polystyrene sufonate (KSodium polystyrene sufonate (K++
binding resin) plusbinding 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 severeHemodialysis as last resort or in severe
casescases

64.  Emergency RxEmergency Rx
– Part A: Shift KPart A: Shift K++
into cellsinto cells
 Will buy you 1-4 hours before directWill 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 1Give 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)

65.  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 2-5Give 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]i
z x F [K]e

67. CALCIOCALCIO
Calcio 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/l
Ca ionizzato v.n. 1,1-1,3 mmol/lQUOTA ATTIVA

68. CalcitoninCalcitonin
and Estrogenand Estrogen Calcium
CalciumParathormoneParathormone
 Ca++ reabsorbing fromCa++ reabsorbing from
the bone back into thethe bone back into the
blood,blood,
 Stimulate renalStimulate renal
reabsorbing of Ca++reabsorbing of Ca++
 Stimulate renalStimulate renal
conversion ofconversion of
Vit D2Vit D2  Vit D3cVit D3c
 Stimulate CalciumStimulate Calcium
deposition in the bonesdeposition in the bones

69. Approach to CalcemiaApproach to Calcemia
 Frazione ionizzata quellaFrazione ionizzata quella ATTIVAATTIVA
 Frazione ionizzata misurataFrazione ionizzata misurata DIRETTAMENTEDIRETTAMENTE
(tentativi di calcolo su pH e proteinemia(tentativi di calcolo su pH e proteinemia
imprecisi)imprecisi) ScambiScambi 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 reciprocoComportamento reciproco Ca e PCa e P
(se prodotto >60 mg/dl(se prodotto >60 mg/dl  Sali cheSali che
precipitano)precipitano)

70. 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)

71. 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)

72.  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 paratiroidisepsis, burns, interventi sulle paratiroidi
 Ipovitaminosi D:Ipovitaminosi D:
apporto inadeguato, malassorbimento, Insuff. Renale,apporto inadeguato, malassorbimento, Insuff. Renale,
EpatopatieEpatopatie Riduzione Turn-over osseo:Riduzione Turn-over osseo:
osteoporosi, invecchiamentoosteoporosi, invecchiamento
 Drugs:Drugs:
EDTA, fenitoina, protamina, gentamicinaEDTA, fenitoina, protamina, gentamicina
Approach to CalcemiaApproach to Calcemia

73. HypocalcemiaHypocalcemia
SymptomsSymptoms
 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 inversionT wave inversion
 Prolonged conductionProlonged conduction
(AV block,(AV block,
AVNRT)AVNRT)

74. AIRWAYS SUPPORTAIRWAYS 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 mg200 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++
administration
Symptomatic IpoCalcemia
Inonized Ca++
< 0,8 mmol/L
Overdosage of Ca++
Channel blocked
Acute symptomaticAcute symptomatic
hypocalcemia treatmenthypocalcemia treatment

75. Hypomagnesemia OverviewHypomagnesemia Overview
 Most of total body MgMost of total body Mg++++
is ICFis ICF
– Serum levels maySerum levels may NOTNOT reflect intracellular statusreflect intracellular status
– Intracellular magnesium depletion has been shown toIntracellular magnesium depletion has been shown to
occur in the setting of decreased, normal, and elevatedoccur in the setting of decreased, normal, and elevated
serum magnesium levelsserum magnesium levels
– If pH increase, improve the legam between Mg andIf 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, cardiacusually neurologic, muscular, cardiac

76. 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

77. HYPOMAGNESEMIAHYPOMAGNESEMIA
Φ4 – Resting
Na+
K+ Na+
Na+
K+
 Quota misurabile minima (max ICF)Quota misurabile minima (max ICF)
 Quota IONIZZATA biologicamente attivaQuota IONIZZATA biologicamente attiva
(50-60% della quota plasmatica)(50-60% della quota plasmatica)
 Se pH aumenta, legame proteico aumenta e quotaSe pH aumenta, legame proteico aumenta e quota
ionizzata si riduce (come Caionizzata si riduce (come Ca++++
))
 Ipo-MgIpo-Mg++++
anche se conc. Plasmatica totale normaleanche se conc. Plasmatica totale normale

78.  Unlike KUnlike K++
replacement, Mgreplacement, Mg++++
replacementreplacement
(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 ofConversion 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++

79.  Housekeeping/follow upHousekeeping/follow up
– BE GENTLEBE GENTLE in patients with acute or chronicin 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 diuresisin DKA patients, IV diuresis
patients, and alcoholicspatients, and alcoholics
 May want to keep magnesium over 2.0 or evenMay want to keep magnesium over 2.0 or even
2.5 mg/dL in cardiac patients, especially in2.5 mg/dL in cardiac patients, especially in
those with arrhythmiasthose with arrhythmias

80. ElectrolytesElectrolytes
 Phosphate (HPhosphate (H22POPO44
--
, HPO, HPO44
2-2-
, PO, PO44
3-3-
))
– 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 acidsalso 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 withRegulation - regulated in an inverse relationship with
CaCa2+2+
by PTH and Calcitoninby PTH and Calcitonin
– Homeostatic imbalancesHomeostatic imbalances
 Phosphate concentrations shift oppositely from calciumPhosphate concentrations shift oppositely from calcium
concentrations and symptoms are usually due to the relatedconcentrations and symptoms are usually due to the related
calcium excess or deficitcalcium excess or deficit

81. Causes of HypophosphatemiaCauses of Hypophosphatemia
 Refeeding syndromeRefeeding syndrome
 DKADKA
 Vitamin D deficiencyVitamin D deficiency
 Malabsorptive syndromesMalabsorptive syndromes
 AlcoholismAlcoholism
 Inadequate TPN dosingInadequate TPN dosing

82. 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 Naor Na++
salts PO BID tosalts 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

83. Grazie per laGrazie per la
CORTESECORTESE
ATTENZIONEATTENZIONE