Clinical approach to patient with Hyperkalemia In internal medicine Causes Clinical findings Complications Treatment

1. Clinical Approach to
Patient with
Hyperkalemia

2. Hyperkalemia is one of the most common electrolytic disorders in
clinical practice. Serum potassium concentration is tightly
regulated by cellular transfer via insulin, catecholamines, and
acid-base equilibrium and secondarily by the kidney via
aldosterone and renal flow. Severe hyperkalemia can result in
dangerous and potentially life-threatening manifestations, mainly
cardiac in nature.
It is therefore crucial for physicians to be able to identify the
causes of hyperkalemia and provide appropriate treatment.
This approach provides an overview of potassium homeostasis,
diagnostic strategies, and treatment guidelines for patients with
mild, moderate, and severe hyperkalemia

3. Pathophysiology
Potassium is the primary intracellular cat ion; 95-98% of the total body
potassium is found in the intracellular space, primarily in muscle. Total
body potassium stores amount to approximately 50 mEq/kg (3500 mEq in
a 70-kg person).
Normal homeostatic mechanisms precisely maintain the serum potassium
level within a narrow range (3.5-5.0 mEq/L). The primary mechanisms for
maintaining this balance are the buffering of extracellular potassium
against a large intracellular potassium pool (via the sodium-potassium
pump), which provides minute-to-minute control, and urinary excretion of
potassium, which determines total body potassium balance.
*

4. Potassium is obtained through the diet. Common
potassium-rich foods include meats, beans and fruits
such as bananas.
Gastrointestinal (GI) absorption is complete, resulting
in daily excess intake of about 1 mEq/kg (60-100
mEq).
Under normal conditions, approximately 90% of
potassium excretion occurs in the urine, with less than
10% excreted through sweat or stool. Within the
kidneys, potassium excretion occurs mostly in the
cortical collecting duct (CCD). Urinary potassium
excretion depends on adequate luminal sodium
delivery to the distal convoluted tubule (DCT) and the
CCD, as well as the effect of aldosterone and other
adrenal corticosteroids with mineralocorticoid activity.

5. DEFINITION :
Hyperkalemia is defined as a plasma potassium level
of 5.5 mM.
It occurs in up to 10% of hospitalized patients;
severe hyperkalemia(>7.0 mM) occurs in
approximately 1%, with a significantly
increased risk of mortality

6. Degrees of hyperkalemia are generally defined as
follows :
5.5-6.0 mEq/L – Mild
6.1-7.0 mEq/L – Moderate
≥7.0 mEq/L – Severe
Levels higher than 7 mEq/L can lead to significant
hemodynamic and neurologic consequences. Levels
exceeding 8.5 mEq/L can cause respiratory paralysis or
cardiac arrest and can quickly be fatal.

7. Causes of Hyperkalemia
1-Pseudohyperkalemia
Hyperkalemia should be distinguished from factitious hyperkalemia or
“pseudohyperkalemia,” an artifactual increase in serum K+ due to the
release of K+ during or after venipuncture- true. Pseudohyperkalemia can
occur in the setting of excessive muscle activity during venipuncture (e.g.,
fist clenching),
A. Cellular efflux: thrombocytosis, erythrocytosis, leukocytosis, in vitro hemolysis
B. Hereditary defects in red cell membrane transport

8. II. Intra- to extracellular shift
A. Acidosis
Acidemia is associated with cellular uptake of H+ and an associated efflux of K+;
it is thought that this effective K+-H+ exchange serves to help maintain
extracellular pH. Notably, this effect of acidosis is limited to non–anion gap
causes of metabolic acidosis and, to a lesser extent, respiratory causes of
acidosis; hyperkalemia due to an acidosis-induced shift of potassium from the
cells into the ECF does not occur in the anion gap acidoses lactic acidosis and
ketoacidosis
B. Hyperosmolality; radiocontrast, hypertonic dextrose, mannitol
Hyperkalemia due to hypertonic mannitol, hypertonic saline, and intravenous
immune globulin is generally attributed to a “solvent drag” effect, as water
moves out of cells along the osmotic gradient
C. β-adrenergic antagonists (noncardioselective agents)
prevent beta-adrenergic stimulation, leading to less potassium uptake, which
may cause hyperkalemia in patients with comorbidities such as renal
insufficiency.

9. D. Digoxin
Digoxin inhibits Na+/K+-ATPase and impairs the uptake of K+ by skeletal muscle,
such that digoxin overdose results in hyperkalemia
E. Hyperkalemic periodic paralysis
F. Lysine, arginine, and ε-aminocaproic acid (structurally similar,
positively
charged)
Cationic amino acids, specifically lysine, arginine,, cause efflux of K+ and
hyperkalemia, through an effective cation-K+ exchange of unknown identity and
mechanism.

10. G. Succinylcholine; thermal trauma, neuromuscular
injury,mucositis, or prolonged immobilization
. Succinylcholine depolarizes muscle cells, causing an efflux of
K+ through acetylcholine receptors (AChRs). The use of this
agent is contraindicated in patients who have sustained
thermal trauma, neuromuscular injury, mucositis, or
prolonged immobilization
H. Rapid tumor lysis
severe tissue necrosis, as in acute tumor lysis syndrome and
rhabdomyolysis, will cause hyperkalemia from the release of intracellular
K

11. III. Inadequate excretion
A. Inhibition of the renin-angiotensin-aldosterone axis; ↑ risk
of hyperkalemia when used in combination
1. Angiotensin-converting enzyme (ACE) inhibitors
2. Renin inhibitors: aliskiren [in combination with ACE-inhibitors
or angiotensin receptor blockers (ARBs)]
3. ARBs
4. Blockade of the mineralocorticoid receptor: spironolactone,
eplerenone
5. Blockade of ENaC: amiloride, triamterene, trimethoprim,
pentamidine
B. Decreased distal delivery
1. Congestive heart failure
2. Volume depletion

12. C. Hyporeninemic hypoaldosteronism
*
1-Tubulointerstitial diseases: systemic lupus erythematosus (SLE),
sicklecell anemia, obstructive uropathy
*
2. Diabetes, diabetic nephropathy
*
3. Drugs: nonsteroidal anti-inflammatory drugs, cyclooxygenase 2
(COX-2)inhibitors, beta blockers, cyclosporine
by multiple mechanisms, but share the ability to cause hyporeninemic
hypoaldosteronism., most drugs that affect the renin-angiotensin-aldosterone axis also
block the local adrenal response to hyperkalemia, thus attenuating the direct stimulation
of aldosterone release by increased plasma K+ concentration
.
*
Inhibition of apical ENaC activity in the distal nephron by amiloride and other K+-sparing
diuretics results in hyperkalemia, often with a voltage-dependent hyperchloremic acidosis
and/or hypovolemic hyponatremia. Amiloride is structurally similar to the antibiotics TMP
and pentamidine, which also block ENaC
.1
4. Chronic kidney disease, advanced age
5. Pseudohypoaldosteronism type II: defects in WNK1 or WNK4 kinases
D. Renal resistance to mineralocorticoid
1. Tubulointerstitial diseases: SLE, amyloidosis, sickle cell anemia, obstructive
uropathy, post-acute tubular necrosis
2. Hereditary: pseudohypoaldosteronism type I: defects in the
mineralocorticoid receptor or ENaC
*

13. *
E. Advanced renal insufficiency
1. Chronic kidney disease
2. End-stage renal disease
3. Acute oliguric kidney injury
F. Primary adrenal insufficiency
1. Autoimmune: Addison’s disease, polyglandular endocrinopathy
2. Infectious: HIV, cytomegalovirus, tuberculosis, disseminated fungal
infection
3. Infiltrative: amyloidosis, malignancy, metastatic cancer
4. Drug-associated: heparin, low-molecular-weight heparin
Among medications associated with hyperkalemia, heparin preparations can cause
selective inhibition of aldosterone synthesis by zona glomerulosa cells, leading to
hyperreninemic hypoaldosteronism
5. Hereditary: adrenal hypoplasia congenita, congenital lipoid adrenal
hyperplasia
6. Adrenal hemorrhage or infarction, including in antiphospholipid
syndrome

14. Finally, Increased intake of even small amounts of K+ may
provoke severe hyperkalemia in patients with predisposing
factors; hence, an assessment of dietary intake is important.
Foods rich in potassium; occult sources of K+, particularly K+-
containing salt substitutes, may also contribute significantly.
Iatrogenic causes include simple over replacement with K+-Cl–
or the administration of a potassium-containing medication (e.g.,
K+- penicillin) to a susceptible patient.
Red cell transfusion is a well- described cause of hyperkalemia,
typically in the setting of massive transfusions

15. History

16. *
Many individuals with hyperkalemia are asymptomatic. When
present, the symptoms of hyperkalemia are nonspecific and
predominantly related to muscular or cardiac function.
*
The most common complaints are weakness and fatigue.
Occasionally, a patient may complain of frank muscle paralysis
or shortness of breath. Patients also may complain of
palpitations or chest pain. Patients may report nausea,
vomiting, and paresthesias. The history is most valuable in
identifying conditions that may predispose to hyperkalemia.
When hyperkalemia is discovered, investigate potential
pathophysiologic mechanisms. For excessive potassium intake,
query patients about the following:
Eating disorders - Very unusual diets consisting almost exclusively of high-
potassium foods, such as fruits (eg, bananas, oranges, or melons), dried fruits,
raisins, fruit juices, nuts, and vegetables with little to no sodium
Heart-healthy diets - Very low–sodium and high-potassium diets recommended
for patients with cardiac disease, hypertension, and diabetes mellitus
Use of potassium supplements in over-the-counter herbal supplements, sports
drinks, dietary supplements

17. With hospitalized patients, review the medication list for potassium
supplements or high-dose penicillin G potassium, and review the
chart to determine whether the patient has received transfusions.
query patients about the following:
Recurrent episodes of flaccid paralysis
Presence of diabetes mellitus
hypertension or angina)
Risk factors for rhabdomyolysis, such as heat stroke, chronic
alcoholism, seizures, sudden excessive exertion (as in military
recruits undergoing basic training)
Risk factors for tumorlysis syndrome, such as ongoing treatment for
widespread lymphoma, leukemia, or other large tumors
Risk factors for hemolysis, such as blood transfusion and sickle cell
disease

18. family history should include questions about the following:
Hyperkalemic periodic paralysis
Deaths of very young siblings
Neuromuscular disorders
Malignant hyperthermia

19. Physical Examination

20. Physical Examination
In patients with hyperkalemia, vital signs generally are normal.
Nonspecific findings can include muscle weakness, fatigue, and
depression. Occasionally, cardiac examination may reveal
extrasystoles, or bradycardia resulting from heart block or
tachypnea resulting from respiratory muscle weakness. Skeletal
muscle weakness and flaccid paralysis may be present, along with
depressed or absent deep tendon reflexes. Patients with ileus may
have hypoactive or absent bowel sounds.
In general, the results of the physical examination alone do not
alert the physician to the diagnosis, except when severe
bradycardia is present or muscle tenderness accompanies muscle
weakness, suggesting rhabdomyolysis. However, when
hyperkalemia has been recognized, evaluation of vital signs is
essential for determining hemodynamic stability and identifying the
presence of cardiac arrhythmias related to the hyperkalemia

21. In a patient who does not have a predisposition to
hyperkalemia, repeat the blood test before taking any actions
to bring down the potassium level, unless changes are present
on electrocardiography (ECG).
Kidney function testing is important. If the patient has kidney
failure, the serum calcium level should be checked
because hypocalcemia can exacerbate cardiac rhythm
disturbances. Other tests include the following:
Electrocardiogram (ECG)
Urine potassium, sodium, and osmolality
Complete blood count (CBC)
Metabolic profile

22. An electrocardiogram (ECG) should be performed in all patients with
asymptomatic serum K > 6 mmol/L and in all patients who are
symptomatic, have rapid-onset hyperkalemia, or have underlying heart,
liver, or kidney disease. Hyperkalemia is associated with a variety of
ECG changes in a dose-dependent manner.
The first sign of hyperkalemia is tall, peaked T waves, usually seen when
K levels are between 5.5-6.5 mmol/L
. Shortened QT and ST segment elevation may follow. As K rises to 7-
8mmol/L or above, disappearance of P waves and QRS complex
widening may develop.
More severe changes can occur with levels > 8 mmol/L, including
conduction blocks, ectopy, or sine wave pattern.
Hyperkalemia may also induce arrythmias, including sinus bradycardia,
ventricular tachycardia, ventricular fibrillation, and asystole.
Though ECG changes may be variable, the rate of potassium rise is a
greater predictor than the potassium serum level itself. For example, a
patient with CKD who has chronically elevated potassium may not show
the same ECG changes as a young type 1 diabetic patient who has an
acute rise in serum potassium because of poor insulin compliance.

23. electrocardiographic manifestations in hyperkalemia

26. Urine Potassium, Sodium, and Osmolality
Measurement of urine potassium and sodium concentrations
and urine osmolality is essential to determine whether
impairment of renal excretion is contributing to the
hyperkalemia. A urine potassium level below 20 mEq/L suggests
impaired renal excretion. A urine potassium level above 40
mEq/L suggests intact renal excretory mechanisms, implying
that high intake or failure of cell uptake is the major
mechanism for hyperkalemia.
A spot urine potassium measurement is the easiest and most
commonly obtained test; a 24-hour urine potassium
measurement is rarely needed.

27. *
Serum and urine osmolality are required for calculation of the
transtubular K+ gradient (TTKG) (Fig. 53-8). The expected
values of the TTKG are largely based on historical data, and are
<3 in the presence of hypokalemia and >7–8 in the presence of
hyperkalemia., some authors have opined that the TTKG does not
consider the effects of distal tubular urea reabsorption on
potassium excretion, concluding that the TTKG is, an unreliable
test in the assessment of hyperkalemia. These are theoretical and
not supported by animal experiments; the TTKG remains a helpful
bedside test of urinary potassium excretion in hyperkalemia
The TTKG is determined by the following equation:
TTKG = (urine K × serum osmolarity)
(serum K × urine osmolarity)
A TTKG of less than 3 suggests a lack of aldosterone effect on the
collecting tubules (that is, the kidneys are not excreting potassium
appropriately). A TTKG greater than 7 suggests an aldosterone
effect, which would be appropriate in the setting of hyperkalemia

28. Treatment of
Hyperkalemia

29. ECG manifestations of hyperkalemia should be considered a
medical emergency and treated urgently. However, patients with
significant hyperkalemia (plasma K+ concentration ≥6.5 mM) in the
absence of ECG changes should also be aggressively managed
Urgent management of hyperkalemia includes admission to the
hospital, continuous cardiac monitoring, and immediate treatment.
The treatment of hyperkalemia is divided into three stages
1-Immediate antagonism of the cardiac effects of
hyperkalemia. Intravenous calcium serves to protect the heart,
whereas other measures are taken to correct hyperkalemia.
Calcium raises the action potential threshold and reduces
excitability, without changing the resting membrane potential. By
restoring the difference between resting and threshold potentials,
calcium reverses the depolarization blockade due to hyperkalemia.
The recommended dose is 10 mL of 10% calcium gluconate (3–4
mL of calcium chloride), infused intravenously over 2–3 min with
cardiac monitoring.
The effect of the infusion starts in 1–3 min and lasts 30–60 min; the
dose should be repeated if there is no change in ECG findings or if
they recur after initial improvement.

30. 2-Rapid reduction in plasma K+ concentration by redistribution into cells.
Insulin lowers plasma K+ concentration by shifting K+ into cells. The recommended
dose is 10 units of intravenous regular insulin followed immediately by 50 mL of 50%
dextrose (D50W, 25 g of glucose total); the effect begins in 10–20 min, peaks at 30–
60 min, and lasts for 4–6 h. Bolus D50W without insulin is never appropriate, given
the risk of acutely worsening hyperkalemia due to the osmotic effect of hypertonic
glucose. Hypoglycemia is common with insulin plus glucose; hence, this should be
followed by an infusion of 10% dextrose at 50–75 mL/h, with close monitoring of
plasma glucose concentration. In hyperkalemic patients with glucose concentrations
of ≥200–250 mg/dL, insulin should be administered without glucose, again with close
monitoring of glucose concentrations
.
β2-Agonists, most commonly albuterol, are effective but underused agents for the
acute management of hyperkalemia. Albuterol and insulin with glucose have an
additive effect on plasma K+ concentration; however, ~20% of patients with ESRD
are resistant to the effect of β2-agonists; hence, these drugs should not be used
without insulin. The recommended dose for inhaled albuterol is 10–20 mg of
nebulized albuterol in 4 mL of normal saline, inhaled over 10 min; the effect starts at
about 30 min, reaches its peak at about 90 min, and lasts for 2–6 h. Hyperglycemia
is a side effect, along with tachycardia. β2- Agonists should be used with caution in
hyperkalemic patients with known cardiac disease
.
Intravenous bicarbonate has no role in the acute treatment of hyperkalemia, but
may slowly attenuate hyperkalemia with sustained administration over several hours.
It should not be given repeatedly as a hypertonic intravenous bolus of undiluted
ampules, given the risk of associated hypernatremia and hyper- tonicity, but should
instead be infused in an isotonic or hypotonic fluid (e.g., 150 milliequivalents of
sodium bicarbonate in 1 L of D5W). In patients with metabolic acidosis, a delayed
drop in plasma K+ concentration can be seen after 4–6 h of isotonic bicarbonate
infusion

31. 3-Removal of potassium. By using cat ion exchange resins,
diuretics, and/or dialysis. The cation exchange resin sodium
polystyrene sulfonate (SPS) exchanges Na+ for K+ in the
gastrointestinal tract and increases the fecal excretion of K+
The recommended dose of SPS is 15–30 g of powder, almost
always given in a premade suspension with 33% sorbitol. The
effect of SPS on plasma K+ concentration is slow; the full effect
may take up to 24 h and usually requires repeated doses every
4–6 h. Intestinal necrosis, typically of the colon or ileum, is a rare
but usually fatal complication of SPS. Intestinal necrosis is more
common in patients with reduced intestinal motility (e.g., in the
postoperative state or after treatment with opioids). The
coadministration of SPS with sorbitol appears to increase the risk
of intestinal necrosis

32. Novel intestinal potassium binders have recently become
available for the management of hyperkalemia. These agents
lack the intestinal toxicity of SPS and are preferred over SPS for
the management of hyperkalemia.
Patiromer is a nonabsorbed polymer provided as a powder for
suspension, which binds K+ in exchange for Ca2+. In healthy
adults, patiromer causes a decrease in urinary potassium,
magnesium, and sodium excretion, suggesting the binding of the
polymer to these cations in the intestine, a major side effect of
the medication is hypomagnesemia.
ZS-9 (sodium zirconium cyclosilicate) is an inorganic,
nonabsorbable crystalline compound that exchanges both Na+
and H+ ions in exchange for K+ and NH4+ in the intestine. These
agents have revolutionized the management of both chronic and
acute hyperkalemia. In particular, the availability of safe, well-
tolerated potassium binders allows for greater intensity of
renin-angiotensin-aldosterone system inhibition in both renal
and cardiac disease

33. Therapy with intravenous saline may be beneficial in
hypovolemic patients with oliguria and decreased distal
delivery of Na+, with the associated reductions in renal K+
excretion. Loop and thiazide diuretics can be used to reduce
plasma K+ concentration in volume-replete or hypervolemic
patients with sufficient renal function for a diuretic response;
this may need to be combined with intravenous saline or
isotonic bicarbonate to achieve or maintain euvolemia
.

34. Hemodialysis is the most effective and reliable method to reduce
plasma K+ concentration; peritoneal dialysis is less effective.. The
amount of K+ removed during hemodialysis depends on the
relative distribution of K+ between ICF and ECF (potentially
affected by prior therapy for hyperkalemia), the type and surface
area of the dialyzer used, dialysate and blood flow rates, dialysate
flow rate,
dialysis duration, and the plasma-to-dialysate K+ gradient

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