Hyperkalemia Flashcards
Hyperkalemia:
Clinical Manifestations
Muscle weakness, cardiac arrhythmias
ECG changes:
Peaked T waves: tall peak (sharp tented) T waves; T wave taller than R wave in ≥2 leads
Hyperkalemia:
Clinical Manifestations
Flattened P waves; Prolonged PR interval
Changes associated with high risk of cardiac arrest: widened QRS complex; merging of S and T waves; bradycardia, idioventricular rhythm; sine wave formation; ventricular fibrillation
Causes and Mechanisms of Hyperkalemia
Pseudohyperkalemia
Pseudohyperkalemia
In vitro (test tube) hyperkalemia, not in vivo hyperkalemia
Correction (treatment) of hyperkalemia is not necessary.
Common conditions associated with pseudohyperkalemia
Causes and Mechanisms of Hyperkalemia
Causes and Mechanisms of Hyperkalemia
Pseudohyperkalemia
Excessive fist clinching with blood draw: exercising (of hand) reduces local ATP and opens up ATP-dependent K+ channels, and allows extracellular K+ shift.
Mechanical trauma, hemolysis with blood draw: release of intracellular K+
Causes and Mechanisms of Hyperkalemia
Pseudohyperkalemia
Thrombocytosis, e.g., for every 100,000 platelets/μL, serum K+ can increase by ~0.15 mEq/L because K+ moves out of platelets after clotting has occurred in test tube. Diagnosis: obtain plasma [K+] (i.e., [K+] measured from blood sample collected in heparin-containing tube to avoid clotting process).
Causes and Mechanisms of Hyperkalemia
Pseudohyperkalemia
If serum [K+] (i.e., [K+] measured in usual manner in nonanticoagulated blood) is greater than P[K+] (i.e., S[K+] − P[K+] > 0.3 mEq/L), pseudohyperkalemia is likely present.
Causes and Mechanisms of Hyperkalemia
Pseudohyperkalemia
Pseudohyperkalemia may also be seen with erythrocytosis and leukocytosis, with the following exception:
“Reverse” pseudohyperkalemia:
Condition where P[K+] > S[K+] (not the usual S[K+] > P[K+] with “regular” pseudohyperkalemia)
Due to cell fragility and lysis with centrifugation, traumatic blood handling (shuttling pneumatic tube system) − heparin-induced K+ leakage from white blood cells
Reported with chronic lymphocytic leukemia
To minimize cell lysis, hand-carry specimen to lab immediately following blood draw and avoid heparin-containing tubes
Causes and Mechanisms of Hyperkalemia
Pseudohyperkalemia
Benign familial (autosomal dominant) pseudohyperkalemia ± associated stomatocytosis: Passive K+ leaks from red blood cells into serum when the blood sample is left at room temperature. This K+ leakage does not occur in vivo. Diagnosis: serial S[K+] measurements while blood is allowed to cool down to normal temperature leads to increasing S[K+] levels.
Increased K+ Input
Dietary: High K+-containing foods, salt substitutes (typical salt-substitute contains 10 to 13 mEq KCl/g or 283 mEq of KCl/tablespoon), mixed fruit juice
K+-containing medications: KCl, high-dose penicillin K, K-citrate, polycitrate
Increased K+ Input
Supplements: fruit/herbal extracts
Red blood cell transfusion due to K+ leakage, particularly problematic with massive transfusions or transfusions of prolonged stored blood
NOTE
Hyperkalemia from intake is not common except in cases of accidental large quantity ingestion, or moderate ingestion in those with poor kidney function and/or reduced mineralocorticoid activity.
Reduced Bodily K+ Loss/Output
Gastrointestinal: severe, chronic constipation with concurrent poor kidney function
Extracellular K+ Shift
Extracellular pH:
Metabolic acidosis:
Inorganic acids (e.g., HCl or sulfuric acid), but not organic acids, cause K+ shift.
Organic acidosis seen with kidney failure or administration of arginine hydrochloride or aminocaproic acid may cause K+ shift.
Extracellular pH:
Metabolic Acidosis:
Lactic acidosis or ketoacidosis has smaller effect on hyperkalemia, partially due to concurrent entry of both anion and hydrogen ion into cells via a sodium-organic anion cotransporter, thus eliminating the need for K+ shifting out of cells to maintain electroneutrality.
Extracellular pH:
Respiratory acidosis:
No significant effect on extracellular K+ shift unless severe and prolonged
Mechanisms for difference on K+ shift compared with metabolic acidosis are not well understood.
Extracellular pH:
Extracellular osmolality:
Increased osmolality (e.g., hyperglycemia, sucrose containing intravenous immune globulin, radiocontrast media, hypertonic mannitol) leads to extracellular K+ shift due to:
Extracellular H2O shift with hyperosmolality increases intracellular K+ concentration, hence greater concentration gradient favoring extracellular shift.
Extracellular H2O shift drags K+ along: “solvent drag” effect.
NOTE
Hyperkalemia is often observed in fasting (e.g., immediate preoperative) blood draws in type 2 diabetic patients. This is thought to be due to the lack of endogenous insulin secretion with fasting, hence reduced insulin-stimulated cellular K+ uptake as well as hyperglycemia/hyperosmolality-inducedhyperkalemia, as described above.
NOTE
To correct this hyperkalemia, administer 5% dextrose (D5) saline solutions ± insulin depending on degree of hyperglycemia. The administration of D5 alone can induce sufficient endogenous insulin secretion and ameliorate hyperkalemia.
Extracellular K+ Shift
Therapy with somatostatin or somatostatin agonist (octreotide) can lead to a fall in insulin and hyperkalemia in susceptible individuals.
Cell death/increased tissue catabolism: e.g., tumor lysis (cytotoxic or radiation therapy), hemolysis, rhabdomyolysis, bowel infarction, soft tissue trauma, severe accidental hypothermia, etc.
Extracellular K+ Shift
Altered Na+-K+-ATPase activity:
Reduced insulin
Reduced β2-adrenergic activity reduces cellular K+ uptake:
- Digitalis overdose (digoxin, ingestion of common oleander or yellow oleander): inhibition of Na+-K+-ATPase
- β-Antagonists and hyperkalemia: (1) inhibits catecholamine-stimulated renin release, hence aldosterone; (2) most important: inhibits Na+-K+-ATPase activity via β2-inhibition. Nonselective agents, therefore, cause more hyperkalemia compared with β1-selective antagonists.
Extracellular K+ Shift
Altered Na+-K+-ATPase activity:
Nonselective β-antagonists: alprenolol, bucindolol, carteolol, carvedilol (+ α-antagonism), labetalol (+ α-antagonism), nadolol, penbutolol, pindolol, propranolol, timolol
Selective β1-antagonists: acebutolol, atenolol, betaxolol, bisoprolol, celiprolol, esmolol, metoprolol, nebivolol
Extracellular K+ Shift
Exercise-induced hyperkalemia:
Delay between K+ exit from cells during depolarization and subsequent cellular reuptake via Na+-K+-ATPase
Exercise-induced reduction in ATP reduces ATP-dependent inhibition of K+-channels, hence more open K+ channels, and increases K+ leak extracellularly.
Extracellular K+ Shift
Exercise-induced hyperkalemia:
Extracellular K+ shift is thought to be adaptive since higher K+ concentration has a vasodilatory effect, hence improved blood flow and energy supply to exercising muscles.
Exercise-induced hyperkalemia is reversed within a few minutes of rest.
Extracellular K+ Shift
ATP-dependent K+ Channels:
Opening of K+ channels leads to K+ efflux:
Lack of ATP as seen with exercise.
Medications: Calcineurin Inhibitors (cyclosporine and tacrolimus), diazoxide, minoxidil, and isoflurane.
Hyperkalemic periodic paralysis:
Autosomal dominant, varying penetrance
Rare channelopathy involving α1-subunit of skeletal muscle Na+ (SCN4A) channels
Hyperkalemic periodic paralysis:
Age of onset: infancy to second decade of life
May be associated with prolonged QT interval (Anderson syndrome), malignant hyperthermia, or paramyotonia congenital von Eulenburg (paradoxical myotonia may be prominent feature, which is worsened with activity or aggressive lowering of S[K+]).
Hyperkalemic periodic paralysis:
Episodic weakness or paralysis may be precipitated by rest after activity, changes in daily level of activity especially in cool temperature, K+ administration
Attacks last 10 to 60 minutes, rarely 1 to 2 days; abrupt paralysis onset may result in falls
Hyperkalemic periodic paralysis:
Stiffness may be aborted with walking, high carbohydrates (candy) intake
S[K+] most often normal, may be high (minimally high), or even low during recovery
Hyperkalemic periodic paralysis:
Diagnosis:
Compound muscle amplitude test
Genetic testing for a small number of mutations available
Hyperkalemic periodic paralysis:
Treatment:
Diet—high carbohydrates, candy; avoid high K+-containing foods; consider diuretics (thiazides, loop diuretics), β-agonists such as albuterol.
Hyperkalemic periodic paralysis:
Administration of succinylcholine to susceptible patients with conditions where there is upregulation of acetylcholine receptors (e.g., neuromuscular disease, severe trauma, burns, chronic immobilization, or infections). Succinylcholine activation of acetylcholine receptors causes cell depolarization and large K+ efflux.
Hyperkalemic periodic paralysis:
Heparin may cause hyperkalemia by several mechanisms:
Inhibition of aldosterone production via reduction in the number and affinity of angiotensin II receptors in zona glomerulosa
Inhibition of the final enzymatic steps of aldosterone formation (18- hydroxylation)
Adrenal hemorrhage
Reduced Renal K+ Loss
Recall renal K+ secretion depends on: (1) distal Na+ delivery, (2) generation of transepithelial potential difference (negative lumen) via Na+ entry into ENaC in principal cells at aldosterone-sensitive distal nephron segment, (3) distal urine flow, (4) presence of aldosterone, (5) sensitivity to aldosterone, and (6) kidney mass.
Reduced Renal K+ Loss
Reduced renal K+ secretion occurs when:
Distal Na+ delivery to cortical and corticomedullary collecting tubules is reduced:
Reduced effective circulating volume (heart failure, cirrhosis, volume depletion, etc.), dietary sodium restriction
Reduced Renal K+ Loss
Diagnosis: clinical history, U[Na+] < 20 mEq/L, improved urinary K+ (U[K+]) excretion with saline infusion
Increased proximal Na+ uptake at distal convoluted tubules, hence reduced Na+ delivery to the more distal collecting tubules (pseudohypoaldosteronism type 2/Gordon syndrome).
Reduced Renal K+ Loss
Reduced generation of transepithelial potential difference (negative lumen) generated by Na+entry into ENaC in principal cells at aldosterone-sensitive distal nephron segment: inhibitors of ENaC—triamterene, amiloride, trimethoprim, pentamidine
Compromised urine flow: obstructive uropathy.
Reduced Renal K+ Loss
Lack of aldosterone:
Hypoaldosteronism: diabetes mellitus → type 4 RTA, primary adrenal insufficiency
Medications: renin angiotensin aldosterone system inhibitors, nonsteroidal anti-inflammatory drugs, COX-2 inhibitors, calcineurin inhibitors, heparin (low molecular weight as well), ketoconazole, drospirenone-containing oral contraceptives (e.g., Yaz, Yasmin): drospirenone has mineralocorticoid antagonist activity
Reduced Renal K+ Loss
Resistance to aldosterone:
Medications: aldosterone antagonists (spironolactone, eplerenone)
a. Pseudohypoaldosteronism type 1 (PHA 1)
1. Hyperkalemia associated with metabolic acidosis and salt-wasting
2. Autosomal dominant form (AD PHA1):
Aldosterone receptor mutation
Treatment: high-dose fludrocortisone, salt supportA
Reduced Renal K+ Loss
Resistance to aldosterone:
- Autosomal recessive form (AR PHA1):
Inactivating mutations in α, β, or γ subunits of ENaC; associated with pulmonary infections
More severe than AD PHA1
Reduced Renal K+ Loss
Resistance to aldosterone:
Salt-wasting in organs requiring ENaC for salt transport (lungs, kidneys, colon, sweat, salivary glands)
High sodium chloride content in sweat and salivary testing
- Treatment: high salt support; NSAIDS have been reported to be beneficial in AR PHA1
Resistance to aldosterone:
Pseudohypoaldosteronism type 2 (Gordon syndrome, a.k.a. familial hyperkalemic hypertension [FHH])
Enhanced paracellular Cl− reabsorption
Enhanced Na+ reabsorption via NaCl cotransporter (NCC) in distal convoluted tubules (DCT), leading to reduced Na+ availability for delivery to cortical collecting tubules (CCT). Reduced Na+ availability at CCT reduces CCT ability to secrete K+ and H+ →hyperkalemia and metabolic acidosis.
Resistance to aldosterone:
Pseudohypoaldosteronism type 2 (Gordon syndrome, a.k.a. familial hyperkalemic hypertension [FHH])
The increased Na+ and Cl− reabsorption leads to volume-expanded state, which suppresses renin angiotensin aldosterone system. Reduced aldosterone also contributes to hyperkalemia and metabolic acidosis.
Resistance to aldosterone:
Pseudohypoaldosteronism type 2 (Gordon syndrome, a.k.a. familial hyperkalemic hypertension [FHH])
Clinical manifestations: hypertension in early adulthood, non-AG metabolic acidosis and hyperkalemia, hypercalciuria, osteoporosis, nephrolithiasis
Resistance to aldosterone:
Pseudohypoaldosteronism type 2 (Gordon syndrome, a.k.a. familial hyperkalemic hypertension [FHH])
Reported NCC regulatory molecules with mutations leading to FHH: with-no-lysine (WNK) 1-4 (inactivating mutations of WNK4 or activating mutations of WNK1), Kelch-Like 3 (KLHL3), and Cullin 3 (CUL3). Mutations in WNK4 also downregulate the transient receptor potential V5 channel (TRPV5, calcium channel) and decrease Ca2+reabsorption in DCT, thus hypercalciuria and osteoporosis. (See Hypertension)
Treatment: thiazide diuretics
Reduced renal K+ secretion occurs when:
Kidney mass/function is reduced:
Reduced overall capacity for renal K+ secretion
Reduced Na+-K+-ATPase activity with uremia, thus reduced cellular uptake
Ureterojejunostomy: increased absorption of urinary K+ by jejunum
Selective impairment of K+ secretion of unclear mechanisms: interstitial disease—lupus nephritis, sickle cell disease
NOTE
Common clinical scenarios with multiple reasons for hyperkalemia:
Diabetic patient: (1) neurogenic bladder leading to urinary stasis; (2) low aldosterone state due to reduced sympathetic stimulation for renin release, adrenal atrophy, and use of renin angiotensin aldosterone inhibitors; and (3) insulin deficiency leading to reduced cellular K+ uptake via Na+-K+-ATPase, hyperosmolality from hyperglycemia leading to cellular K+ efflux, metabolic acidosis with diabetic ketoacidosis leading to K+efflux, and hypovolemia leading to reduced Na+ delivery to collecting tubules
Patient with cirrhosis or heart failure: (1) use of spironolactone, (2) low effective circulating volume leading to poor Na+ delivery to collecting tubules, and (3) recurrent kidney injuries
Management of Hyperkalemia: Temporizing Measures
For patients with relatively good kidney function and nonthreatening ECG changes, consider volume resuscitation with normal saline and administration of loop diuretics.
Management of Hyperkalemia: Temporizing Measures
For severe hyperkalemia with high-risk ECG changes and kidney failure, emergent hemodialysis is indicated.
Consider nutritional consult for low-K+ diet if applicable.
Good bowel regimen and other emergent
Treatment of Hyperkalemia
