What is
hyperkalemia?
Hyperkalemia is a serious medical
condition characterised by excessive
serum K+ levels.1
What is hyperkalemia?
K+ homeostasis is vital1—6
K+ is the most abundant cation in the body.1 Approximately 2% of the
body’s K+ is in extracellular fluid, with 98% in the intracellular space.2,3
- This concentration gradient is partially responsible for membrane
potential and is critical for normal cell function3–5 - Its maintenance is therefore particularly important for excitable
cells such as nerve, muscle, and cardiac myocytes5,6
Regulation of K+ balance
The primary mechanism of K+ homeostasis occurs at the renal
level via the renin-angiotensin-aldosterone system7
Following a dietary potassium load, robust homeostatic mechanisms help maintain
normal K+ concentrations to avoid excessive K+ influx into the extracellular fluid.7
Feedback control
The aldosterone-dependent negative feedback loop
regulates extracellular K+ homeostasis by increasing
renal excretion of K+ to maintain normal K+ levels.8
Muscle K+ uptake
Insulin regulates the intracellular homeostasis of K+
through activating the transmembrane enzyme
Na-K-ATPase, pumping K+ into the cell in
exchange for Na+ out of the cell.8
Feedforward control
The gut-to-kidney signalling pathway is thought to
play an important role in K+ homeostasis, although
the kaliuretic factor is not yet fully understood.8
Hyperkalemia is typically defined as elevated
serum K+ levels >5.0 mEq/L1,4
Chronic hyperkalemia is defined as serum K+ levels >5.0 mEq/L repetitively measured over 1 year.9
Normokalemia is typically defined as serum K+ levels
between 3.5 mEq/L and 5 mEq/L.4
Mild, moderate, and severe hyperkalemia is
defined as serum K+ levels of >5–5.5, >5.5–6.0 and
>6.0 mEq/L, respectively.4
What causes hyperkalemia?
Hyperkalemia is caused by a complex interplay of
physiological and environmental factors10,11
The kidneys are responsible for 90% of potassium excretion. The most
common underlying cause of hyperkalemia is reduced or impaired renal
excretion of K+, leading to a build-up of extracellular K+ levels.12
Chronic kidney disease
In CKD, K+ homeostasis, established mostly by
excretion of K+ via urine, is deregulated and can
result in hyperkalemia.
Heart failure
In HF, RAASi is up-regulated, renal perfusion is
reduced and Na+ is often excreted due to usage
of diuretics.
Diabetes mellitus
Due to the lack of insulin-stimulated Na+–K+
pump-mediated K+ uptake in skeletal muscles.
Age
Age-dependent reduction in the availability of
nephrons further increases the risk for hyperkalemia.
Medication
Background use of RAASi, beta blockers and
aldosterone antagonists are associated with
an increase in K+ levels.
Exercise
Because skeletal muscles constitute the major
reservoir for K+ levels which may increase markedly
and reach values up to ~8 mEq/L during exercise.
Intake of K+
Oral K+ intake combined with reduced K+
excretion can increase risk of hyperkalemia.
Discover the mechanisms of hyperkalemia
in CKD and HF
Why monitoring K+ is important
The asymptomatic nature of hyperkalemia makes
diagnosis extremely difficult1
Although some patients with hyperkalemia may present with symptoms such as muscle twitching, cramping, or nausea,10,13 hyperkalemia is often left unnoticed until patients experience serious consequences.1
- It is important to regularly monitor your patient’s serum K+ levels, do not wait for symptoms to develop as the clinical consequences can be fatal
- Laboratory monitoring is critical to diagnose hyperkalemia as ECG changes are unreliable (particularly in CKD patients)14
ECG changes are not always present in patients with hyperkalemia making it difficult to detect. Additionally, ECG changes can rapidly progress without warning. The combination of hyperkalemia and ECG changes is a medical emergency.1
Idealised model of ECG features corresponding to the degree of hyperkalemia7
Normokalemia
Moderate hyperkalemia
Severe hyperkalemia
This is an idealised model of ECG features, it is important to note there is a poor correlation between ECG features and the degree of hyperkalemia7
Hyperkalemia can have serious consequences7,15—18
The consequences of hyperkalemia on myocardial excitability are well established.7 However, emerging evidence is
highlighting the potential role of hyperkalemia in the manifestation of other serious clinical consequences.7,15—18
- Hyperkalemia has been shown to impair ammoniagenesis in the proximal renal tubule.7
- Net renal acid excretion relies on ammonium, with low rates of ammonium excretion causing subnormal acid excretion.18
- The combination of hyperkalemia and impaired renal acid excretion is called type IV renal tubular acidosis.7
- A causal relationship between serum K+ and axonal depolarisation has been identified in dialysis patients,17 with pre-dialysis axonal depolarisation occurring with serum K+ levels ~5.4 mEq/L.7
- These findings suggest hyperkalemia-induced depolarisation may have an important role in the development of uremic neuropathy.7,17
- Aldosterone secretion is stimulated following an increase in plasma potassium,15 with an incremental relationship between changes in serum K+ and plasma aldosterone.15
- Excessive aldosterone is associated with many deleterious health consequences, including the cardiovascular system, brain and kidneys, through promoting endothelial dysfunction, tissue fibrosis and inflammation.16
- As serum K+ increases beyond 5.0 mEq/L, the cell membrane of cardiac cells become partially depolarised. The shift in cellular polarisation drives the resting potential near the threshold potential for action potential initiation.7
- As a consequence, fast sodium channels (Nav1.5) are activated more readily, increasing myocardial excitability and conduction velocity.7
Discover the consequences of
hyperkalemia in CKD
Discover the consequences of
hyperkalemia in HF
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