Using lectures to identify student misconceptions: a study on the paradoxical effects of hyperkalemia on vascular smooth muscle.

Medical students have difficulty understanding the mechanisms underlying hyperkalemia-mediated local control of blood flow. Such control mechanisms are crucial in the brain, kidney, and skeletal muscle vasculature. We aimed to identify medical students' misconceptions via assessment of students' in-class knowledge and, subsequently, improve future teaching of this concept. In-class polling was performed with the TurningPoint clicker response system (n = 860) to gauge students' understanding of three physiological concepts related to hyperkalemia: membrane potential (Vm), conductance, and smooth muscle response. Vm includes the concepts of equilibrium potential (Veq) for specific ions, as well as driving force (DF = Vm - Veq). Students understood the concept of DF (~70% answered correctly), suggesting their understanding of Vm. However, students misunderstood that hyperkalemia results in depolarization (~52% answered correctly) and leads to an increase in potassium conductance (~31% answered correctly). Clarification of the type of smooth muscle as vascular increased the percentage of correct responses (~51 to 73%). The data indicate that students lacked knowledge of specific potassium conductance in various muscle types, resulting in divergent responses, such as the canonical depolarization in skeletal muscle versus hyperpolarization in smooth muscle cells during hyperkalemia. Misunderstanding of this crucial concept of conductance is directly related to the students' performance. Furthermore, we connected the paradoxical effect of hyperkalemia to pathological acute and chronic hyperkalemia clinical scenarios.

A physiology-based approach to a patient with hyperkalemic renal tubular acidosis / Abordagem diagnóstica de um paciente com acidose tubular renal hipercalêmica

ABSTRACT Hyperkalemic renal tubular acidosis is a non-anion gap metabolic acidosis that invariably indicates an abnormality in potassium, ammonium, and hydrogen ion secretion. In clinical practice, it is usually attributed to real or apparent hypoaldosteronism caused by diseases or drug toxicity. We describe a 54-year-old liver transplant patient that was admitted with flaccid muscle weakness associated with plasma potassium level of 9.25 mEq/L. Additional investigation revealed type 4 renal tubular acidosis and marked hypomagnesemia with high fractional excretion of magnesium. Relevant past medical history included a recent diagnosis of Paracoccidioidomycosis, a systemic fungal infection that is endemic in some parts of South America, and his outpatient medications contained trimethoprim-sulfamethoxazole, tacrolimus, and propranolol. In the present acid-base and electrolyte case study, we discuss a clinical approach for the diagnosis of hyperkalemic renal tubular acidosis and review the pathophysiology of this disorder.

RESUMO A acidose tubular renal hipercalêmica é uma acidose metabólica de ânion gap normal que invariavelmente indica anormalidade na secreção de íons potássio, amônio e hidrogênio. Na prática clínica, está geralmente atribuída a um estado de hipoaldosteronismo real ou aparente, causado por doenças ou toxicidade por drogas. Descrevemos um paciente de 54 anos, transplantado hepático, que foi admitido com fraqueza muscular associada à hipercalemia, potássio plasmático de 9,25 mEq/L. A investigação adicional revelou acidose tubular renal tipo 4 e importante hipomagnesemia com elevada fração de excreção de magnésio. A história patológica pregressa incluía um diagnóstico recente de Paracoccidioidomicose - uma infecção sistêmica fúngica endêmica que ocorre em algumas partes da América do Sul -, e as medicações de uso habitual continham sulfametoxazol-trimetoprim, tacrolimus e propranolol. No presente relato de caso, discutiremos uma abordagem clínico-laboratorial para o diagnóstico da acidose tubular renal hipercalêmica, assim como da hipomagnesemia, revisando a fisiopatologia desses transtornos.

A physiology-based approach to a patient with hyperkalemic renal tubular acidosis.

Hyperkalemic renal tubular acidosis is a non-anion gap metabolic acidosis that invariably indicates an abnormality in potassium, ammonium, and hydrogen ion secretion. In clinical practice, it is usually attributed to real or apparent hypoaldosteronism caused by diseases or drug toxicity. We describe a 54-year-old liver transplant patient that was admitted with flaccid muscle weakness associated with plasma potassium level of 9.25 mEq/L. Additional investigation revealed type 4 renal tubular acidosis and marked hypomagnesemia with high fractional excretion of magnesium. Relevant past medical history included a recent diagnosis of Paracoccidioidomycosis, a systemic fungal infection that is endemic in some parts of South America, and his outpatient medications contained trimethoprim-sulfamethoxazole, tacrolimus, and propranolol. In the present acid-base and electrolyte case study, we discuss a clinical approach for the diagnosis of hyperkalemic renal tubular acidosis and review the pathophysiology of this disorder.

Evidence-Based Management Of Potassium Disorders In The Emergency Department.

Hypokalemia and hyperkalemia are the most common electrolyte disorders managed in the emergency department. The diagnosis of these potentially life-threatening disorders is challenging due to the often vague symptomatology a patient may express, and treatment options may be based upon very little data due to the time it may take for laboratory values to return. This review examines the most current evidence with regard to the pathophysiology, diagnosis, and management of potassium disorders. In this review, classic paradigms, such as the use of sodium polystyrene and the routine measurement of serum magnesium, are tested, and an algorithm for the treatment of potassium disorders is discussed.

Evidence-based management of potassium disorders in the emergency department [digest].

Hypokalemia and hyperkalemia are the most common electrolyte disorders managed in the emergency department. The diagnosis of these potentially life-threatening disorders is challenging due to the often vague symptomatology a patient may express, and treatment options may be based upon very little data due to the time it may take for laboratory values to return. This review examines the most current evidence with regard to the pathophysiology, diagnosis, and management of potassium disorders. In this review, classic paradigms, such as the use of sodium polystyrene and the routine measurement of serum magnesium, are tested, and an algorithm for the treatment of potassium disorders is discussed. [Points & Pearls is a digest of Emergency Medicine Practice].

In silico ischaemia-induced reentry at the Purkinje-ventricle interface.

AIMS: This computational modelling work illustrates the influence of hyperkalaemia and electrical uncoupling induced by defined ischaemia on action potential (AP) propagation and the incidence of reentry at the Purkinje-ventricle interface in mammalian hearts. METHODS AND RESULTS: Unidimensional and bidimensional models of the Purkinje-ventricle subsystem, including ischaemic conditions (defined as phase 1B) in the ventricle and an ischaemic border zone, were developed by altering several important electrophysiological parameters of the Luo-Rudy AP model of the ventricular myocyte. Purkinje electrical activity was modelled using the equations of DiFrancesco and Noble. Our study suggests that an extracellular potassium concentration [K(+)]o >14 mM and a slight decrease in intercellular coupling induced by ischaemia in ventricle can cause conduction block from Purkinje to ventricle. Under these conditions, propagation from ventricle to Purkinje is possible. Thus, unidirectional block (UDB) and reentry can result. When conditions of UDB are met, retrograde propagation with a long delay (320 ms) may re-excite Purkinje cells, and give rise to a reentrant pathway. This induced reentry may be the origin of arrhythmias observed in phase 1B ischaemia. CONCLUSION: In a defined setting of ischaemia (phase 1B), a small amount of uncoupling between ventricular cells, as well as between Purkinje and ventricular tissue, may induce UDBs and reentry. Hyperkalaemia is also confirmed to be an important factor in the genesis of reentrant rhythms, since it regulates the range of coupling in which UDBs may be induced.

The metabolic and toxicological considerations for immunosuppressive drugs used during pancreas transplantation.

INTRODUCTION: Pancreas-kidney transplant is an effective treatment for patients with insulin-dependent dabetes and chronic renal failure. Reduction in technical failure loss and early acute rejection rates contributed to prolong pancreas graft survival. However, drug toxicity affects negatively both short- and long-term follow-ups. AREAS COVERED: This article reviews the existing literature and knowledge of the immunosuppressive drugs that are frequently used in pancreas transplant, including calcineurin inhibitors, sirolimus, corticosteroids, and mycophenolate. The article also discusses the short- and long-term adverse effects of these drugs. The article also reports and discusses the most relevant in vitro studies, providing additional information to in vivo findings. Some clinically relevant drug interactions with immunosuppressive drugs are also highlighted. Over- and underimmunosuppression effects will not be addressed. EXPERT OPINION: Immunosuppressive regimen after pancreas transplant is very effective and contributed to pancreas allograft survival. However, they present several side effects that are potentiated when drugs are combined. Modifiable and non-modifiable risk factors can aggravate metabolic and toxicological effects of immunosuppressive drugs. It is important to critically analyze the results of clinical studies and investigate new immunosuppressive drugs and/or novel drug combinations. It is equally important to comprehend and interpret experimental data. Therefore, minimization of side effects, based on safe approaches, can prolong pancreas allograft survival.

Understanding the risk of hyperkalaemia in heart failure: role of aldosterone antagonism.

The risk of hyperkalaemia in patients with heart failure has increased in the past few years together with the evolution of pharmacological treatment for these patients. This significant change has been associated with the introduction of angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and aldosterone antagonists. High potassium concentrations in heart failure could lead to life threatening events, and therefore should be taken seriously. In this review we summarise the information about potassium homeostasis in heart failure and the current risk of developing potentially serious hyperkalaemia, particularly in association with the use of aldosterone antagonists.

Bloqueo AV completo, reversible, en relación a hiperkalemia grave por enalapril y espironolactona: caso clínico / Complete atrioventricular block, reversible, related to serious hyperkalemia due to enalapril and spironolactone: case report

La hiperkalemia es una de las principales complicaciones potenciales del uso de drogas del tipo IECA, bloqueadores ARAII y antagonistas del receptor de aldosterona, en relación a su dosis, su eventual uso combinado y la función renal del paciente. A continuación se reporta el caso de un paciente de 71 años de edad, hipertenso y diabético que se encontraba en tratamiento con Enalapril 10 mg c/12 h y Furosemida 40 mg a/ 12 h, que sufre una bloqueo aurículo ventricular de 3º grado, secundario a una hiperkalemia de 8.53 mEq/l.

Potassium metabolism in extremely low birth weight infants in the first week of life.

OBJECTIVE: Nonoliguric hyperkalemia has been reported to occur in the first week of life in as many as 50% of extremely low birth weight (ELBW) infants. We studied potassium balance and renal function in the first 5 days of life to characterize potassium metabolism during the three phases of fluid and electrolyte homeostasis that we have described in ELBW infants and to elucidate the factors that contribute to the development of nonoliguric hyperkalemia. STUDY DESIGN: Plasma potassium concentration (PK), potassium intake and output, and renal clearances were obtained for the first 6 days of life in 31 infants with a birth weight of 1000 gm or less. Collection periods in which urine flow rate was greater than or equal to 3 ml/kg per hour and weight loss was greater than or equal to 0.8 gm/kg per hour were denoted to be diuretic. Prediuresis includes all collection periods before the first diuretic period; diuresis includes all collection periods between the first and last diuretic periods; postdiuresis includes all collection periods after the last diuretic period. Infants with a PK greater than 6.7 mmol/L on at least one measurement were denoted to have hyperkalemia. RESULTS: PK increased initially after birth--despite the absence of potassium intake- and then decreased and stabilized by the fourth day of life. Diuresis occurred in 27 of 31 infants. The age at which PK peaked was closely related to the onset of diuresis. PK decreased significantly during diuresis as the result of a more negative potassium balance, despite a significant increase in potassium intake. In fact, PK fell to less than 4 mmol/L in 13 of 27 infants during diuresis. After the cessation of diuresis, potassium excretion decreased even though there was a significant increase in potassium intake, potassium balance was zero, and PK stabilized. Hyperkalemia developed in 11 of 31 infants. The pattern of change in PK with age was similar in infants with normokalemia and hyperkalemia: PK initially increased (essentially in the absence of potassium intake) and then decreased and stabilized by the fourth day of life. However, the rise in PK after birth was greater in infants with hyperkalemia than in those with normokalemia: 0.7 +/- 0.2 versus 1.8 +/- 0.2 mmol/L (p < 0.001). No differences in fluid and electrolyte homeostasis or renal function were identified as associated with hyperkalemia. CONCLUSIONS: PK increases in most ELBW infants in the first few days after birth as a result of a shift of potassium from the intracellular to the extracellular compartment. The increase in the glomerular filtration rate and in the fractional excretion of sodium, with the onset of diuresis, facilitates potassium excretion, and PK almost invariably decreases. Hyperkalemia seems to be principally the result of a greater intracellular to extracellular potassium shift immediately after birth in some ELBW infants.

Utilizaçäo de marcadores de DNA para o diagnóstico genômico de animais domésticos: 2. Detecçäo da mutaçäo pontual causadora da Paralisia Hipercalêmica Periódica (HYPP) em equinos da raça Quarto de Milha / Use of DNA markers for genomic diagnosis of domestic animals: 2. Detection of point mutation causing Hyperkalemic Periodic Paralysis (HYPP) in Quarter horses

Analisaram-se 12 equinos da raça Quarto de Milha, descendentes da linhagem Impressive. Submeteram-se os DNAs purificados a partir de leucócitos destes animais, à técnica de Polymerase Chain Reaction (PCR) e posterior digestäo com a enzima de restriçäo Taq I. Estabeleceu-se, dessa maneira, o diagnóstico genômico da Paralisia Hipercalcêmica Periódica (HYPP). Os exames revelaram que 9 animais eram portadores heterozigotos (N/H) e 3, normais homozigotos (N/N). A partir do desenvolvimento da metodologia de PCR tornou-se possível diagnosticar o problema e propor maneiras de controle do alastramento desse gene defectivo na populaçäo por meio da detecçäo de animais portadores e normais

Síndrome de hipoaldosteronismo hiporreninémico / Hyporrheninemic hypoaldosteronism syndrome

El hipoaldosteronismo hiporreninémico es un síndrome que no es infrecuente en la práctica clínica, pero que indudablemente es subdiagnosticado. Constituye la mitad de los casos de hiperkalemia inexplicada, por lo que es un diagnóstico que siempre debe tenerse presente, sobre todo en pacientes diabéticos con algún grado de insuficiencia renal. El diagnóstico se confirma con la medición de aldosterona plasmática y la actividad de renina plasmática, en presencia de una función glucocorticoidea normal. Se presenta un caso clínico de hipoaldosteronismo hiporreninémico, cuyo diagnóstico fue sospechado a través de una hiperkalemia asintomática de etiología inexplicada, el que fue confirmado por los exámenes pertinentes y cuyo tratamiento con diuréticos resultó exitoso

Duchenne-Becker muscular dystrophy and the nondystrophic myotonias. Paradigms for loss of function and change of function of gene products.

Recessively inherited disorders can most often be considered loss of function: the patient has only defective copies of the defective gene (homozygous or hemizygous), with little or no functional protein products produced. Dominantly inherited disorders can most often be considered change of function: the patient has both mutant and normal copies of the gene (heterozygous); however, the mutant gene produces an abnormal protein product that causes dysfunction of the cell. Categorization of inherited disorders simply by their inheritance pattern thus affords some predictions concerning the underlying biochemical defect. To illustrate these generalizations, the molecular data on two important human inherited neurologic disorders will be described. X-linked recessive Duchenne/Becker muscular dystrophy has been shown to caused by loss of function of the dystrophin product. Dominantly inherited hyperkalemic periodic paralysis and paramyotonia congenita have been shown to be the result of single amino acid changes of the skeletal muscle voltage-sensitive sodium channel that alter the channel's function in response to environmental or physiologic stimuli (change of function).

[Correction of hyperkalemia with intravenous salbutamol in children with chronic renal insufficiency]. / Corrección de la hiperkalemia con salbutamol endovenoso en niños con insuficiencia renal crónica.

In order to evaluate the efficiency of albuterol sulfate (salbutamol) in lowering of potassium levels in uremic children with hyperkalemia, we intravenously administered salbutamol 30 micrograms/min (total doses 0.5 mg) to ten children with chronic renal failure (CRF) with high serum levels of potassium. Forty five minutes after administration, potassium serum levels were lower going from 6.79 +/- 0.57 mmol/L to 5.04 +/- 1.10 mmol/L; increasing levels were documented 6 hours later up to 5.76 +/- 0.66 mmol/L. Lowering in potassium serum levels was associated with disappearance of electrocardiographic manifestations of hyperkalemia. We observed moderated tachycardia in 90% of our patients and only one patient required withdrawal of this drug for high cardiac frequency rate. We conclude that salbutamol is a useful and safe choice in treatment of hyperkalemia in children with CRF.