1. HIPOKALEMIA
Leal Lam Sara Li
Clínica 475
Nefrología
UNIVERSIDAD AUTÓNOMA DE BAJA CALIFORNIA
Escuela de Ciencias de la Salud
Campus Valle de las Palmas
2. POTASIO
• Catión que determina el potencial de
membrana en reposo
• Total: 3500 mmol
• 98% intracelular (3430 mmol)
• 2% extracelular (70 mmol)
• 2 sistemas homeostáticos de
regulación:
• Equilibrio interno
• Equilibrio externo
• Ingestión = excreción
5. HIPOKALEMIA
• Se refiere a una concentración
plasmática de potasio baja.
• <3.5 mEq/L
• Epidemiología:
• Dietas altas en Na o bajas en K
• Tx con diuréticos (50%)
• Hiperaldosteronismo
6. ETIOLOGÍA
• Medicamentos,
producción
hormonal
endógena, defectos
• Sudoración
excesiva, diarrea
crónica, vómitos
• Contenido de K
• Hormonas,
catecolaminas,
acidosis, ejercicio
• Desplazamientos a
través de la
membrana celular
• Leucemia aguda
•↓K artificial
Pseudohipokalemi
a
Redistribución
Pérdida renal de K
Pérdida extrarrenal
de K
8. MANIFESTACIONES
CLÍNICAS
Hipokalemi
a
Arritmias
cardíacas con
anormalidades
en el ECG
Alteraciones de la
conducción
(parálisis o
hiperexcitabilidad
)
Debilidad
muscular,
calambres,
rabdomiólisis,
mioglobinuria
Diarrea
HTA, alteración
en reabsorción de
Na, ↓capacidad
de concentración,
↑producción de
amonio,
↑reabsorción de
HCO3Se afecta el potencial de membrana en
reposo
<2.5 mEq/L
12. TRATAMIENTO
K+ sérico % pérdidas K+ total Tratamiento
Normal 3.5-5 mEq/L
0%
K+ total: 48 mEq/kg
-
Leve 3-3.4 mEq/L 5% o 300 mEq
Dieta + suplementos
orales
Moderado 2.5-3 mEq/L 10% o 400 mEq Tx VO/ IV
Grave <2.5 mEq/L ≥15% o >500 mEq Tx IV
Por cada 100 mEq totales
perdidos, el K+ sérico ↓0.27
mEq/L
13. REGLAS DE REPOSICIÓN
1. Administración por vía periférica no mayor a 40 mEq/L.
2. Administración por vía central no mayor a 100 mEq/L.
3. La velocidad de infusión no debe sobrepasar los 10-20 mEq/h.
4. No administrar más de 200 mEq/día.
5. Control de K sérico a las 6-8 h.
6. Toma de ECG previa a la administración de K.
7. Verificar diuresis antes de la administración de K.
8. Mantener monitorizado al paciente cuando se repone K por vía
endovenosa.
9. Control estricto de líquidos administrados-eliminados.
10. Siempre diluir K en SSN 0.9%.
14. SOLUCIONES
Solución Indicaciones
Vía de
administración
Aporte Administración
Bicarbonato de K
-Acetato de K: único
IV
Hipokalemia +
acidosis metabólica
IV
2-4 mEq/ml
(20, 50, 100 ml)
-IV: 40-100 mEq/día
-Infusión intermitente IV*: 5-10 mEq/dosis
(máx. 40 mEq/dosis) a infundir cada 2-3 h
(máx. 40 mEq en 1 h)
Fosfato de K
Hipokalemia +
hipofosfatemia
IV
4.4 mEq K + 3 mmol/ml P
170 mg K + 93 mg P
Dosis baja: 0.08 mmol/kg cada 6 horas
KCl
En todos los pacientes
con hipokalemia
VO; IV
VO: 1 cápsula= 8 mEq
IV: 5 mEq (250 ml sol. salina
0.9%)
750 mg KCl= 10 mEq
Variable
Máx. cct. Para infusión periférica: 10 mEq K/
100 mL, con máx. vel. de administración 10
mEq/hora
Gluconato de K Hipokalemia leve VO 1 g gluconato de K= 4.3 mEq 1 tableta diaria
15. REPLECIÓN DE POTASIO
Vía de
administración
de KCl
Indicaciones
Dosis máx./ tasa
de repleción
Efectos
secundarios
Oral
2.5-3.4 mEq/L +
Fx GI conservada
40 mEq cada 2-3
h
Malestar GI
IV:
-vía periférica
-vía central
<2.5 mEq/L
-VP: 10 mmol/
hora
-VC: 20-40 mmol/
hora
Dolor en zona de
punción
16. TRATAMIENTO URGENTE
Indicaciones
•Parálisis hipokalémica transitoria
•Hipokalemia severa
•IAM
Protocolo a seguir
•5-10 mmol KCl x 15-20 minutos
•Repetir dosis cuantas veces sea necesario
•Monitoreo de K+ sérico y ECG
Complicación
•Hiperkalemia letal aguda
17. BIBLIOGRAFÍA
• Costanzo, L. Fisiología 4ta edición. Editorial Elsevier. 2011.
• Gilbert S., Weiner D. National Kidney Foundation: Primer on Kidney Disease.
Editorial Elsevier. 2013.
• Johson R., Feehally J., Floege J. Comprehensive Clinical Nephrology. Editorial
Elsevier. 2014.
• Mount D. Clinical manifestations and treatment of hypokalemia in adults.
Wolters Kluwer. 2016.
• Mount D. Evaluation of the adult patient with hypokalemia. Wolters Kluwer.
2016.
• Sterns R. Hypokalemia- induced renal dysfunction. Wolters Kluwer. 2016.
• Prutkin J. ECG tutorial: Miscellaneous diagnoses. Wolters Kluwer. 2016.
Hinweis der Redaktion
El mantenimiento del equilibrio del potasio (K+) es básico para la función normal de los tejidos excitables (p. ej. nervio, músculo esquelético, músculo cardíaco). El gradiente de concentración de K+ a través de las membranas celulares excitables determina el potencial de membrana en reposo. Así pues, los cambios en el potencial de membrana en reposo modifican la excitabilidad al abrir o cerrar compuertas en los canales de Na+, que se encargan de la fase de ascenso del potencial de accion. Los cambios en la concentración intracelular o extracelular de K+ alteran el potencial de membrana en reposo y, en consecuencia, modifican la excitabilidad de estos tejidos. La mayor parte del K+ corporal total se encuentra en el LIC: el 98% del contenido total de K+ esta en el compartimento intracelular y el 2% esta en el compartimento extracelular. Una consecuencia de esta distribucion es que la concentracion intracelular de K+ (150 mEq/l) es mucho mayor que la extracelular (4.5 mEq/l). Este gran gradiente de concentracion de K+ es mantenido por la Na+-K+ ATPasa, que se encuentra en todas las membranas celulares.
Two homeostatic systems help to maintain potassium homeostasis. The first system regulates potassium excretion (kidney and intestine). The second regulates potassium shifts between the extracellular and intracellular fluid compartments.
Regulación externa:
-Plasma potassium is freely filtered across the glomerular capillary into the proximal tubule. It is subsequently completely reabsorbed by the proximal tubule and loop of Henle. In the distal tubule and the collecting duct, potassium is secreted into the tubular lumen. For practical purposes, urinary excretion of potassium reflects potassium secretion into the lumen of the distal tubule and collecting duct. Thus, any factor that stimulates potassium secretion increases urinary potassium excretion; conversely, any factor that inhibits potassium secretion decreases urinary potassium excretion.
-Five major physiologic factors stimulate distal potassium secretion and increase excretion: aldosterone; high distal sodium delivery; high urine flow rate; high [K+] in tubular cell; and metabolic alkalosis.
Regulación interna:
-Extracellular fluid [K] is ~4 mEq/L, whereas the intracellular [K] is ~150 mEq/L. Because of the uneven distribution of potassium between the fluid compartments, a relatively small net shift of potassium from the intracellular to the extracellular fluid compartment produces marked increases in plasma potassium. Conversely, a relatively small net shift from the extracellular to the intracellular fluid compartment produces a marked decrease in plasma potassium. Whereas renal excretion of potassium requires several hours, potassium shift between the extracellular and intracellular fluid compartment (also referred to as extrarenal potassium disposal) is extremely rapid, occurring within minutes.
-The two major physiologic factors that stimulate transfer of potassium from the extracellular to the intracellular fluid compartments (in) are insulin and epinephrine. The stimulation of extrarenal potassium disposal by insulin and β2-adrenergic agonists are both mediated by the Na,K-ATPase activity, primarily in skeletal muscle cells. Interference with these two physiologic mechanisms (insulin deficiency or β2- adrenergic blockade, respectively) predisposes to hyperkalemia. On the other hand, excessive insulin or epinephrine levels predispose to hypokalemia.
The potassium-lowering effect of insulin is dose-related within the physiologic range of plasma insulin and is independent of its effect on plasma glucose.
The potassium-lowering action of epinephrine is mediated by β2-adrenergic stimulation, and it is blocked by nonselective β-blockers, but not by selective β1-adrenergic blockers. Alpha-adrenergic stimulation promotes shifts of potassium out of cells into the extracellular fluid compartment, tending to increase serum potassium. Epinephrine is a mixed alpha- and β-adrenergic agonist, such that its net effect on serum potassium reflects the balance between its β-adrenergic (potassium-lowering) and alpha-adrenergic (potassium-raising) effects. In normal individuals the β-adrenergic effect of epinephrine predominates over the alpha-adrenergic effect, and the result is a fall in the serum potassium. In contrast, the alpha-adrenergic effect of epinephrine on potassium shifts is more prominent in patients with kidney failure; as a result, dialysis patients are refractory to the potassium-lowering effect of epinephrine.
-Acid-base disorders produce internal potassium shifts in a less predictable manner. As a general rule, metabolic alkalosis shifts potassium into the cells, whereas metabolic acidosis shifts potassium out of the cells. However, the nature of the metabolic acidosis determines its effect on serum potassium. Cells are relatively impermeable to chloride. With inorganic acidosis, entry of protons (but not chloride) into the cell results in a reciprocal extrusion of potassium out of the cell to maintain electric neutrality. In contrast, cells are highly permeable to organic anions. The addition of an organic acid to the extracellular fluid results in parallel shifts of protons and organic anions into the cells with no net change in the electric balance; as a result, potassium is not extruded from the cells. Thus, mineral acidosis (i.e., hyperchloremic, normal anion gap metabolic acidosis) typically results in hyperkalemia, whereas organic metabolic acidosis (e.g., lactic acidosis) does not affect the serum potassium concentration. Bicarbonate administration to individuals with normal kidney function decreases serum potassium, but this effect is largely due to enhanced urinary excretion of potassium.
Hipokalemia ≠ deficiencia de K.
Deficiencia de K: is the state resulting from a persistent negative potassium balance, that is, potassium excretion exceeding potassium intake.
Hipokalemia: refers to a low plasma potassium concentration. Hypokalemia can be due either to potassium deficiency (inadequate potassium intake or excessive potassium losses) or to net potassium shifts from the extracellular to the intracellular fluid compartment.
Medications Both thiazide and loop diuretics increase urinary potassium excretion, and the incidence of diuretic-induced hypokalemia is related to both dose and treatment duration. If the effect of loop and thiazide diuretics on sodium excretion is compared and adjusted, thiazide diuretics actually cause more urinary potassium loss than loop diuretics. Certain antibiotics increase urinary potassium excretion. Some penicillin analogues, such as piperacillin/ tazobactam, increase distal tubular delivery of a non-reabsorbable anion, which obligates the presence of a cation such as potassium, thereby increasing urinary potassium excretion. The antifungal agent amphotericin B directly increases collecting duct potassium secretion. Aminoglycosides may cause hypokalemia either with or without simultaneous nephrotoxicity. The mechanism is incompletely understood but may relate to magnesium depletion (see later discussion). Cisplatin is a common antineoplastic agent that can induce hypokalemia. Toluene exposure, from sniffing certain glues, can also cause renal tubular acidosis with renal potassium wasting, leading to hypokalemia.27 In addition, certain herbal products, including herbal cough mixtures, licorice tea, licorice root, and gan cao, contain glycyrrhizic and glycyrrhetinic acids, which have mineralocorticoid-like effects.
Endogenous Hormones Endogenous hormones are important and common causes of hypokalemia. Aldosterone is the most important hormone regulating total body potassium homeostasis. Aldosterone causes hypokalemia both by stimulating potassium uptake into cells and by stimulating renal potassium excretion. Primary aldosteronism is a common cause of hypokalemia.
Genetic Causes Genetic defects leading to excessive aldosterone production are occasionally seen as causes of renal potassium wasting (see Chapter 49). Glucocorticoid-remediable aldosteronism (GRA) is a condition in which a corticotropin (ACTH)–regulated promoter is linked to the gene for aldosterone synthase, the ratelimiting enzyme for aldosterone synthesis.29 As a result, aldosterone synthase expression is regulated by ACTH, leading to excessive aldosterone synthase expression and the development of severe hyperaldosteronism. In congenital adrenal hyperplasia, there is persistent adrenal synthesis of 11-deoxycorticosterone, a potent mineralocorticoid. 30 This condition can be recognized by the associated effects on sex steroid production. Genetic defects can also lead to abnormal activation of the mineralocorticoid receptor, resulting in the same clinical manifestations as excessive aldosterone production. The glucocorticoid hormone cortisol can activate the mineralocorticoid receptor. Under normal conditions, the enzyme 11β-hydroxysteroid dehydrogenase, type 2 (11β-HSDH-2) rapidly metabolizes cortisol to cortisone, thereby preventing inappropriate mineralocorticoid receptor activation.31 If this does not occur, glucocorticoid hormones are able to activate mineralocorticoid receptors. Genetic deficiency of 11β-HSDH-2 is rare, but leads to severe hypertension and hypokalemia. Some compounds, such as glycyrrhetinic acid, found in some chewing tobacco and licorice preparations, inhibit 11β-HSDH-2, allowing cortisol to exert mineralocorticoid-like effects.32 Also, in severe Cushing syndrome circulating cortisol levels can exceed the metabolic capacity of 11β-HSDH-2, resulting in mineralocorticoid receptor activation and hypokalemia.
Magnesium Depletion Magnesium deficiency inhibits renal potassium retention and causes inappropriately high renal potassium excretion despite hypokalemia. This occurs most frequently as a complication of prolonged diuretic use and can also result from aminoglycoside- and cisplatin-induced renal toxicity. Magnesium deficiency should be suspected when potassium replacement does not correct hypokalemia; treatment with magnesium replacement generally reverses the potassium wasting.
Intrinsic Renal Defect Intrinsic renal potassium transport defects leading to hypokalemia are rare but have led to important advances in our understanding of renal solute transport.
Bartter syndrome is characterized by hypokalemia, reduced blood pressure, hyperreninemia, metabolic alkalosis, and hypercalciuria. Patients with Bartter syndrome typically develop clinical manifestations at a young age, which include severe volume depletion and growth retardation. Bartter syndrome results from genetic abnormalities in any of several proteins involved in sodium and potassium transport in the thick ascending limb of the loop of Henle.
Gitelman syndrome is similar to Bartter syndrome, except patients have hypocalciuria and milder clinical manifestations and are usually diagnosed later in life. Gitelman syndrome results from genetic abnormalities in the proteins involved in distal convoluted tubule sodium and potassium transport.36 When Bartter or Gitelman syndrome is suspected, it is critical to evaluate the patient for surreptitious diuretic use, because loop and thiazide diuretics give the same clinical phenotype as Bartter and Gitelman syndrome, respectively.
Liddle syndrome is characterized by severe hypertension, hypokalemia and suppressed renin and aldosterone levels. Liddle syndrome is caused by a mutation that increases collecting duct ENaC expression and activity, leading to excessive sodium reabsorption, potassium excretion, volume expansion, and hypertension.
Pérdida extrarrenal de K:
Sudoración excesiva: se pierden ¿?
Vómitos:
Diarrea:
According to the Nernst equation, the resting membrane potential is related to the ratio of the intracellular to the extracellular potassium concentration. In skeletal muscle, a reduction in the serum (extracellular) potassium concentration will increase this ratio and therefore hyperpolarize the cell membrane (that is, make the resting potential more electronegative); this impairs the ability of the muscle to depolarize and contract, leading to weakness. However, in some cardiac cells (such as Purkinje fibers in the conducting system), hypokalemia causes K2P1 channels, which are normally selective for potassium, to transport sodium into the cells, causing depolarization [16,17]. This leads to increased membrane excitability and arrhythmias. Hypokalemia also delays ventricular repolarization by inhibiting the activity of potassium channels responsible for this component of the cardiac electrical cycle.
Alteraciones renales:
Menor capacidad de concentración de iones en la orina:Está asociado a menor respuesta a la hormona antidiurética (ADH) en el túbulo colector, pero no se conoce bien el mecanismo de acción. 2 factores que pueden contribuir son menor expresión de acuaporina-2 (canal de agua que actúa bajo la influencia de la ADH) y menor actividad del transportador Na-K-2Cl en el asa ascendente de Henle (que tiene un rol central en el gradiente contracorriente)
Aumento en la producción de amonio: Debido a bajo K sérico, el K+ intracelular sale de las células y, para mantener la electroneutralidad, entra H+ en su lugar. Esto genera acidosis intracelular, lo que hace que se produzca mucho más amonio a partir de la glutamina para compensar la acidez intracelular.
Aumento en la reabsorción de HCO3: La acidosis intracelular (descrita anteriormente) inducida por hipokalemia promueve un aumento en la secreción de H+, el cual reacciona con el HCO3 luminal, lo que provoca que se consuma y las células “reclamen” HCO3 y la absorban más para evitar que se consuma completamente en su intento por compensar la acidez luminal.
Alter. En reabsorción de Na: se altera la bomba Na-K ATPasa, que al no tener K sérico, el Na no se excreta y además aumenta su reabsorción en TCP. Esto genera expansión del volumen sanguíneo y eleva moderadamente la presión arterial (hasta 5 mmHg), un efecto que puede ser importante en Px con HTA.
HTA:
According to the Nernst equation, the resting membrane potential is related to the ratio of the intracellular to the extracellular potassium concentration. In skeletal muscle, a reduction in the serum (extracellular) potassium concentration will increase this ratio and therefore hyperpolarize the cell membrane (that is, make the resting potential more electronegative); this impairs the ability of the muscle to depolarize and contract, leading to weakness. However, in some cardiac cells (such as Purkinje fibers in the conducting system), hypokalemia causes K2P1 channels, which are normally selective for potassium, to transport sodium into the cells, causing depolarization. This leads to increased membrane excitability and arrhythmias.
Hypokalemia also delays ventricular repolarization by inhibiting the activity of potassium channels responsible for this component of the cardiac electrical cycle.
Significado onda U:
When the U wave exceeds the T wave amplitude, then the serum K+ level is more likely to be <3 mEq/L.
La dieta normal aporta 70-150 mmol/día.
K+ total:
3400 mEq o 48 mEq/kg
Administración por vía periférica no mayor a 4 mEq/h. Mayor a esto es riesgo de flebitis.
Administración por vía central no mayor a 40 mEq/h.
La velocidad de infusión no debe sobrepasar los 20 mEq/L.
No administrar más de 200 mEq/día. Debido a riesgo de dañar endotelio vascular y para evitar hiperkalemia de rebote en aquellos casos donde la hipokalemia es transitoria.
Control de K a las 6 h.
Toma de ECG previa a la administración de K. Con motivos de evaluación al Px (ver si responde a Tx, evolución del Px, pronóstico, si se está llegando o no a hiperkalemia, etc).
Verificar diuresis antes de la administración de K. En la hipokalemia suele haber ↓flujo urinario para evitar mayores pérdidas de K. También se hace para revisar si no hay evolución a insuficiencia renal (que provoca anuresis).
Mantener monitorizado al paciente cuando se repone K por vía endovenosa.
Control estricto de líquidos administrados-eliminados.
Siempre diluir K en SSN 0.9%.
El Tx tiene 3 metas: prevenir o tratar las complicaciones que pongan en riesgo la vida del Px (arritmias, parálisis, rabdomiólisis, debilidad diafragmática), reemplazar el déficit de K, y tratar la enfermedad de base. El reemplazo de K es el pilar del Tx.
As with any condition, the risks associated with untreated or slowly treated hypokalemia must be balanced against the risks of therapy. Usually, the primary short-term risks are cardiovascular arrhythmias and neuromuscular weakness. Overaggressive therapy can cause acute hyperkalemia, which can cause ventricular fibrillation and sudden death.
In the great majority of hypokalemic patients, emergency therapy is not necessary, and instead a slower approach to replacing the potassium deficit is appropriate. In doing so, it is important to recognize that the amount of potassium required may be much greater than predicted from the deficit in serum potassium concentration. This occurs because the body responds to chronic hypokalemia resulting from potassium losses by shifting potassium from ICF to ECF compartment, thereby minimizing the change in extracellular [K+]. Consequently, the amount of potassium replacement needed is much greater than predicted by the change in extracellular [K+] and the ECF volume.
Potassium replacement can be given through the intravenous (IV) or oral (PO) route. Oral or enteral administration is preferred if the patient can take oral medication and has normal GI tract function. Acute hyperkalemia is highly unusual when potassium is given orally. This reflects several factors, most prominently gut sensors that minimize changes in serum potassium levels. When potassium is given intravenously, acute hyperkalemia can occur if the IV rate is too rapid and can cause sudden cardiac death. IV replacement can be given safely at a rate of 10 mmol KCl/h. Intravenous KCl should not be administered more quickly than 10 mmol/h in the absence of continuous ECG monitoring. The serum potassium should be rechecked every 2 to 3 hours to confirm a clinical response and to avoid an overshoot.
Although significant variations can occur between patients, IV administration of 20 mmol KCl typically increases the serum potassium by about 0.25 mmol/l. If more rapid replacement is necessary, 20 or 40 mmol/h can be administered through a central venous catheter, but continuous ECG monitoring should be used under these circumstances.
