Acid-base and Potassium Disorders in Children, Part 2

Educational Objectives

The goal of this program is improve the diagnosis and treatment of potassium disorders. After hearing and assimilating this program, the clinician will be better able to:

1. Cite major causes of hyperkalemia and hypokalemia.
2. Implement a treatment strategy for hyperkalemia.

Summary

Potassium (K) balance: 90% of dietary K is absorbed (affected by gut motility); absorption is increased in patients who have ileus or constipation; insulin and epinephrine provide protection against acute increases in serum K (drive K into cells to prevent life-threatening hyperkalemia); most K is stored intracellularly; therefore, plasma K levels may not reflect total body stores; K shifts between intracellular and extracellular spaces can have a major impact on serum K levels

Regulators of transcellular K shifts: alkalosis, insulin, and β-agonists can drive K into cells; exercise, hemolysis, rhabdomyolysis, and acidosis drive K out of cells; in acidosis, K is exchanged for hydrogen ions, which helps to buffer the blood

Aldosterone: most K is reabsorbed in the proximal segments of the nephron, with mediation by the Na-K-2 chloride cotransporter (NKCC2); aldosterone regulates excretion of the 10% of K that reaches the collecting duct (promotes secretion of K in exchange for Na); mechanism — aldosterone enters the cell and binds to the mineralocorticoid receptor (which increases the abundance and activity of epithelial Na channels [ENaC), leading to reabsorption of Na; K leaks back via the rectifying outer medullary K (ROMK) channel

Hyperkalemia

Causes: may be spurious, ie, pseudohyperkalemia may be caused by hemolysis of the blood sample, an increase in the number of platelets (an increase of 100,000/μL increases the K level by 0.15 mEq/L), or leukocytosis; increased intake of K rarely is the cause; causes related to transcellular shifts — acidosis; rhabdomyolysis; hemolytic anemia; internal bleeding; tumor lysis syndrome

Decreased excretion: chronic kidney disease (CKD); insufficient aldosterone (eg, hypoaldosteronism); drugs that interfere with the renin-angiotensin-aldosterone system; resistance to aldosterone — may result from type 4 renal tubular acidosis [RTA]), postobstructive hyperkalemia (eg, after correction of posterior urethral valves), sickle cell disease, or pseudohypoaldosteronism type I (a genetic mutation in ENaC); presents with salt wasting, blood pressures in the low-normal range, hyperkalemia, and mild metabolic acidosis (type 4 RTA)

Importance of diagnosis: patients with hyperkalemia may remain asymptomatic until ventricular fibrillation (VF) develops or may present in asystole; classic electrocardiographic (ECG) findings include a peak T wave (an enlarged T wave that appears peaked), the absence of P waves, and widening of the QRS before development of VF; however, these ECG changes are not sufficiently sensitive or specific for diagnosis of hyperkalemia (confirmed hyperkalemia should be treated regardless of whether typical ECG findings are present)

Treatment goals: initially, to prevent arrhythmias; the secondary goal is removal of K from the body

Prevention of arrhythmia: initially, administer intravenous Ca to stabilize the heart muscle; follow with insulin plus glucose (most effective treatment; drives K into the cells), then β-agonists (most effective when given at high doses, eg, albuterol at 2-4 times the normal dose; not used alone because they are ineffective in 30%-40% of patients); administer sodium bicarbonate only if a patient has significant acidemia (do not use empirically); the onset of action of these interventions is within minutes; however, as they do not remove K, levels begin to rise immediately after their discontinuation

Delayed interventions: include diuretics; sodium polystyrene (a K binder) may be used in patients with good urine output (contraindicated for patients with history of abdominal surgery or ileus because of risk for colonic necrosis); dialysis (if feasible) in patients with CKD

Hypokalemia

Causes of K loss: extrarenal — diarrhea (associated with acidosis); vomiting or skin losses in cystic fibrosis (associated with alkalosis and low urine Cl); transcellular shifts — include alkalemia or use of insulin or β-agonists; renal — include hypomagnesemia and chemotherapy that causes tubular injury

Acid-base status in renal loss of K: alkalosis with high urine Cl — consider diuretics, Bartter syndrome, and Gitelman syndrome; alkalosis with hypertension — consider hyperaldosteronism and Liddle syndrome (gain-of-function mutation of the ENaC; the opposite of pseudohypoaldosteronism type I); acidosis — consider proximal and distal RTA

Disruption of NKCC2: also causes Ca wasting and hypercalciuria (kidney stones and nephrocalcinosis); occurs with pharmacologic blockade (eg, loop diuretics) or genetic mutation (Bartter syndrome), which result in Na wasting, K wasting, metabolic alkalosis, and high urine Cl

Disruption of the NaCl cotransporter (NCC): occurs with genetic mutation (Gitelman syndrome) or pharmacologic blockade (use of thiazide diuretics); manifests with hypocalciuria

Increased activity of the ENaC: occurs with true hyperaldosteronism or genetic mutation (Liddle syndrome); manifests with Na retention (causing hypertension), K wasting, and metabolic alkalosis

Rare causes: glucocorticoid remediable aldosteronism — linked to a chimeric gene that directs adrenocorticotropic hormone to bind to the aldosterone-promoting region, releasing aldosterone; treated with spironolactone; syndrome of apparent mineralocorticoid excess — results from a mutation involving the enzyme that degrades cortisol (cortisol, rather than aldosterone, causes hypertension); also treated with spironolactone

Clinical manifestations: arrhythmias (less common than in hyperkalemia) such as torsades de pointes; common if the patient is taking digoxin or has prolonged QT); polyuria; muscle weakness (skeletal muscle weakness and rhabdomyolysis or smooth muscle weakness in the ileus causing constipation); ECG findings — U waves, flattened T waves and ST depression

Readings

Enslow BT et al. Liddle's syndrome mechanisms, diagnosis and management. Integr Blood Press Control. 2019;12:13-22. Published 2019 Sep 3. doi:10.2147/IBPC.S188869; Hunter RW, Bailey MA. Hyperkalemia: pathophysiology, risk factors and consequences. Nephrol Dial Transplant. 2019;34(Suppl 3):iii2-iii11. doi:10.1093/ndt/gfz206; Kovesdy CP. Updates in hyperkalemia: Outcomes and therapeutic strategies. Rev Endocr Metab Disord. 2017;18:41-47; doi: 10.1007/s11154-016-9384-x; Palmer BF, Clegg DJ. Physiology and pathophysiology of potassium homeostasis. Adv Physiol Educ. 2016;40:480-490; doi: 10.1152/advan.00121.2016; Palmer BF, Clegg DJ. Diagnosis and treatment of hyperkalemia. Cleve Clin J Med. 2017;84:934-942; doi: 10.3949/ccjm.84a.17056; Unwin RJ et al. Pathophysiology and management of hypokalemia: a clinical perspective. Nat Rev Nephrol. 2011;7:75-84; doi: 10.1038/nrneph.2010.175.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose. In his lecture, Dr. Bou Matar presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Bou Matar was recorded at the 26th Annual Pediatric Board Review, held virtually August 30 to September 4, 2020, and presented by the Cleveland Clinic Foundation. For information on future CME activities from this presenter, please visit www.clevelandclinicmeded.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

PD673302

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.