hyperkalemia

1. HYPERKALEMIA
Dr. Prateek Singh
Jr1 medicine
TUTH

2. Brief review of potassium physiology
and homeostasis
• An understanding of potassium physiology is helpful when
approaching patients with hyperkalemia.
• Total body potassium stores are approximately 3000 meq or
more (50 to 75 meq/kg body weight). which is primarily an
intracellular cation, with the cells containing approximately 98%
of body potassium.
• The intracellular potassium concentration is approximately 140
meq/L compared with 4 to 5 meq/L in the extracellular fluid.

3. • The difference in distribution of the two cations is maintained by
the Na-K-ATPase pump in the cell membrane which pumps
sodium out of and potassium into the cell in a 3:2 ratio.
• The plasma potassium concentration is determined by the
relationship among ;
 Potassium intake,
 The distribution of potassium between the cells and the
Extracellular fluid, and
 Urinary potassium excretion.

4. Regulation of urinary potassium
excretion
• In normal individuals, dietary potassium is absorbed in the
intestines and then largely excreted in the urine 90%
• This process is primarily determined by potassium
secretion by the principal cells in the two segments that
follow the distal tubule: the connecting segment and
cortical collecting tubule

5. • There are three major factors that stimulate principal cell
potassium secretion:
1. An increase in plasma potassium concentration and/or
potassium intake
2. An increase in aldosterone secretion.
3. Enhanced delivery of sodium and water to the distal
potassium secretory sites.

6. • Ingestion of a potassium load initially leads to the uptake
of most of the excess potassium by cells in muscle and
the liver.
 Some of the ingested potassium remains in the
extracellular fluid, producing a mild elevation in the
plasma potassium concentration.
 The increase in plasma potassium stimulates the
secretion of aldosterone, which directly enhances sodium
reabsorption and indirectly enhances potassium secretion
in the principal cells.

7. Hyperkalemia is a rare occurrence in normal individuals because
the cellular and urinary responses prevent significant potassium
accumulation in the extracellular fluid. Furthermore, the
efficiency of potassium excretion is enhanced if potassium
intake is increased.
This phenomenon, called potassium adaptation, is mostly due
to the ability to more rapidly excrete potassium in the urine.
The increased efficiency of potassium excretion with potassium
adaptation appears to be mediated by the changes that occur in
the potassium-secreting principal cells in the connecting
segment and cortical collecting tubule
Potassium adaptation.

8. The increase in plasma potassium stimulates the secretion of aldosterone, which directly
enhances sodium reabsorption and indirectly enhances potassium secretion in the
principal cells.The increase in sodium reabsorption is mediated primarily by an increase in
the number of open sodium channels in the luminal membrane of the principal cells.The
reabsorption of cationic sodium makes the lumen more electronegative, thereby
enhancing the electrical gradient that promotes the secretion of potassium from the cells
into the tubular fluid via potassium channels in the luminal membrane. Aldosterone also
increases the number and activity of basolateral Na-K-ATPase pumps in principal cells,
which facilitates both sodium reabsorption and potassium secretion. The net effect is
that most of the potassium load is excreted within six to eight hours.

9. Conclusions from the preceding observation of potassium
physiology and homeostasis concerning the causes of
hyperkalemia.
1. Increasing potassium intake alone is not a common cause of
hyperkalemia unless it occurs acutely which can rarely be
induced by
• Administration of potassium penicillin as an intravenous
bolus.
• The Accidental ingestion of a potassium-containing salt
substitute.
• The use of stored blood for exchange transfusions.
In addition, moderate increases in potassium intake can be an
important contributor to the development of hyperkalemia in
patients with impaired potassium excretion due to eg.
hypoaldosteronism and/or renal insufficiency.

10. 2. The net release of potassium from the cells (due to enhanced
release or decreased entry) can, if large enough (eg,
increased tissue breakdown), cause a transient elevation in
the serum potassium concentration.
3. Persistent hyperkalemia requires impaired urinary
potassium excretion.
This is generally associated with a reduction in aldosterone
secretion or responsiveness, acute or chronic kidney disease,
and/or diminished delivery of sodium and water to the distal
potassium secretory sites.

11. Hyperkalemia is defined as a plasma potassium level of > 5.5
mM, occuring in up to 10% of hospitalized patients.
Severe hyperkalemia (>6.0 mM) occurs in approximately 1%,
with a significantly increased risk of mortality.
Although redistribution and reduced tissue uptake can
acutely cause hyperkalemia, a decrease in renal K+ excretion
is the most frequent underlying cause.
Excessive intake of K+ is a rare cause, given the adaptive
capacity to increase renal secretion.
HYPERKALEMIA

14. Artifactual increase in serum K+ due to the release of K+ during or
after venipuncture.
suspected when
•no apparent cause for the hyperkalemia in an asymptomatic
patient who has no ECG manifestations of hyperkalemia.
•Causes
1. excessive muscle activity during venipuncture (eg fist clenching)
by more than 1 to 2 meq/L in that forearm
2 . Marked increase in cellular elements (thrombocytosis,
leukocytosis, and/or erythrocytosis) with in vitro efflux of K+.
3. acute anxiety during venipuncture with respiratory alkalosis and
redistributive hyperkalemia
Pseudohyperkalemia

15.  Cooling of blood following venipuncture is another cause, due
to reduced cellular uptake; the converse is the increased
uptake of K+ by cells at high ambient temperatures, leading
to normal values for hyperkalemic patients and/or to spurious
hypokalemia in normokalemic patients.
 There are multiple genetic subtypes of hereditary
pseudohyperkalemia, caused by increases in the passive K+
permeability of erythrocytes. Eg. , causative mutations have
been described in the red cell anion exchanger (AE1, encoded
by the SLC4A1 gene), leading to reduced red cell anion
transport, hemolytic anemia, the acquisition of a novel AE1-
mediated K+ leak, and pseudohyperkalemia.

16. I. INTRA TO EXTRACELLULAR SHIFT
• Metabolic Acidosis.
Uptake of H+,efflux ofK+ mainly in non anion gap
metabolic acidosis.Which does not occur in the organic
acidoses lactic acidosis and ketoacidosis. A possible contributory
factor is the ability of the organic anion and the hydrogen ion to
enter into the cell via a sodium-organic anion cotransporter.

17.  Insulin deficiency, hyperglycemia and
hyperosmolality —
this frequently leads to hyperkalemia even though there
may be marked potassium depletion due to urinary
losses caused by the osmotic diuresis. Hyperosmolality
results in osmotic water movement from the cells into
the extracellular fluid thereby creating a favorable
gradient for passive potassium exit through potassium
channels in the cell membrane and solvent drag
phenomenon which is independent of the gradient for
potassium diffusion.

18. • β2-Adrenergic antagonists
interfere with the beta-2-adrenergic facilitation of potassium
uptake by the cells, particularly after a potassium load. An
increase in serum potassium is primarily seen with nonselective
beta blockers (such as propranolol and labetalol). In contrast,
beta-1-selective blockers such as atenolol have little effect on
serum potassium since beta-2 receptor activity remains intact
• Digoxin and related glycosides (yellow oleander,
foxglove)
causing dose-dependent inhibition of the Na-K-ATPase pump

19. • Succinylcholine
depolarises Muscle cells causes Efflux of K+ throughAChRs .
Contraindicated in thermal trauma, neuromuscular injury, disuse
atrophy, mucositis,or prolonged immobilization because of upregulated
AChRs
• Cationic amino acids, specifically lysine, arginine,
and the structurally related drug epsilon-aminocaproic acid
entry into the cells presumably obligates potassium exit to
maintain electroneutrality.

20. • Rapid tumor lysis / Rhabdomyolysis/ Massive blood
transfusion
• Use of drugs that activate ATP-dependent potassium
channels in cell membranes, such as calcineurin inhibitors
(eg, cyclosporine and tacrolimus), diazoxide, minoxidil, and
several volatile anesthetics (eg, isoflurane)
• Hyperkalemic periodic paralysis
Hyperkalemic periodic paralysis is an autosomal dominant
disorder in which episodes of weakness or paralysis are
usually precipitated by cold exposure, rest after exercise,
fasting, or the ingestion of small amounts of potassium.The
most common abnormality in hyperkalemic periodic paralysis
is a point mutation in the gene for the alpha subunit of the
skeletal muscle cell sodium channel.

21. II. REDUCED URINARY POTASSIUM
EXCRETION
Urinary potassium excretion is primarily mediated by potassium
secretion in the principal cells.
The four major causes of hyperkalemia due to reduced urinary
potassium secretion are:
• Reduced aldosterone secretion
• Reduced response to aldosterone (aldosterone resistance)
• Reduced distal sodium and water delivery as occurs in effective
arterial blood volume depletion
• Acute and chronic kidney disease in which one or more of the
above factors are present

23. Pseudohypoaldosteronism type 1
Pseudohypoaldosteronism type 1 is a rare hereditary disorder
that is characterized by aldosterone resistance.The autosomal
recessive form affects the collecting tubule sodium channel
(ENaC) , and the autosomal dominant form in most patients
affects the mineralocorticoid receptor. symptoms Hyponatremia,
volume depletion, hyperkalemia

24.  Pseudohypoaldosteronism type 2 (Gordon's syndrome)
An inherited syndrome of hyperkalemia, volume
expansion, hypertension, and otherwise normal renal
function has been called pseudohypoaldosteronism type 2,
Gordon's syndrome, or familial hyperkalemic
hypertension.The reduction in aldosterone secretion
represents an appropriate response to volume expansion.
 Defects in WNK1 orWNK4 kinases proteins that localize to the distal nephron
and affect the thiazide-sensitive Na-Cl cotransporter, Kelch-like 3 (KLHL3), or
Cullin 3 (CUL3).

25. Reduced distal sodium and water delivery
The most common cause of reduced distal sodium and water
delivery is effective arterial blood volume depletion,
Effective arterial blood volume depletion includes any cause of
true volume depletion (eg, gastrointestinal or renal losses) as well
as heart failure and cirrhosis in which decreased tissue perfusion
is due to a reduced cardiac output and vasodilation, respectively.
other potentially important contributing factors to hyperkalemia
in patients with heart failure and cirrhosis include angiotensin
inhibitor therapy in heart failure and aldosterone antagonists in
both heart failure and cirrhosis.

26.  Advanced renal insufficiency
Chronic kidney disease
Acute oliguric kidney disease
 Hyperkalemia is most commonly seen in patients who are
oliguric or have an additional problem such as a high-
potassium diet, increased tissue breakdown, reduced
aldosterone secretion or responsiveness, or fasting in dialysis
patients which may both lower insulin levels and cause
resistance to beta-adrenergic stimulation of potassium uptake
 Advanced renal failure retained uremic toxins may decrease
the transcription of mRNA for the alpha1 isoform of the Na-K-
ATPase pump in skeletal muscle causeing diminished Na-K-
ATPase activity

27. Most of Hyperkalemic individuals are asymptomatic.
The most serious manifestations of hyperkalemia are
• muscle weakness or paralysis,
• cardiac conduction abnormalities, and cardiac arrhythmias.
These manifestations usually occur when the serum potassium
concentration is ≥7.0 mEq/L with chronic hyperkalemia or
possibly at lower levels with an acute rise in serum potassium.
Patients with skeletal muscle or cardiac manifestations typically
have one or more of the characteristic ECG abnormalities
associated with hyperkalemia.
Clinical Features

28. Hyperkalemia can cause ascending muscle weakness that begins
with the legs and progresses to the trunk and arms.This can
progress to flaccid paralysis, mimicking Guillain-Barré syndrome
to differentiate it from familial hyperkalemic periodic paralysis
(HYPP).
The presentation may include diaphragmatic paralysis and
respiratory failure. Patients with familial HYPP develop
myopathic weakness during hyperkalemia induced by increased
K+ intake or rest after heavy exercise.
Muscle weakness or paralysis

29. Hyperkalemia is a medical emergency due to its effects on the
heart.
Cardiac arrhythmias associated with hyperkalemia include
• sinus bradycardia, sinus arrest,
• slow idioventricular rhythms,
• ventricular tachycardia,
• ventricular fibrillation, and asystole.
Cardiac manifestation

30. 1. Mild increases in extracellular K+ affect the
repolarization phase of the cardiac action potential,
resulting in changes inT-wave morphology.
2. Further increase in plasma K+ concentration
depresses intracardiac conduction, with progressive
prolongation of the PR and QRS intervals.
3. Severe hyperkalemia results in loss of the P wave and
a progressive widening of the QRS complex,
development of a sine-wave sinoventricular rhythm
suggests impending ventricular fibrillation or asystole.

31. Classically, the ECG manifestations in hyperkalemia progress from
• tall peakedT waves (5.5–6.5 mM), to
• a loss of P waves (6.5–7.5 mM) to
• a widened QRS complex (7.0–8.0 mM), and,

32. • ultimately, to a sine wave pattern (>8.0 mM).
• for untreated hyperkalemia is chaotic depolarisation of ventricular myocardium:
ventricular fibrillation.
However, these changes are notoriously insensitive, particularly in
patients with chronic kidney disease or end-stage renal disease.

33. Hyperkalemia can also cause a type I Brugada pattern in the
ECG, with a pseudo–right bundle branch block and persistent
coved ST segment elevation in at least two precordial leads.
This hyperkalemic Brugada’s sign
occurs in critically ill patients with
severe hyperkalemia and can be
differentiated from genetic
Brugada’s syndrome by
• an absence of P waves,
• marked QRS widening, and
• an abnormal QRS axis.

34. DIAGNOSTIC APPROACH TO HYPERKALEMIA
Tests In Evaluation of Hyperkalemia
The first priority in the management of hyperkalemia is to assess
the need for emergency treatment, followed by a
comprehensive workup to determine the cause
• History on medications, diet, risk factors for kidney
failure, reduction in urine output, blood pressure,
volume status.
• BUN, creatinine, serum osmolarity
• Serum Electrolytes- including Mg, Ca
• Urine potassium, sodium, and osmolality
• Trans-tubular potassium gradient (TTKG)
• Complete blood count (CBC)
• ECG

35. Trans-tubular potassium gradient (TTKG)
TTKG is an index reflecting the conservation of
potassium in the cortical collecting ducts (CCD) of the
kidneys.
It is useful in diagnosing the causes of hyperkalemia or
hypokalemia.
The expected values of theTTKG are largely based on
historical data, and are <3 in the presence of hypokalemia
and >7–8 in the presence of hyperkalemia.
TTKG estimates the ratio of potassium in the lumen of the
CCD to that in the peritubular capillaries.
TTKG= Urine K/ Serum K x serum Osm/Urine osm

36. APPROACHTO HYPERKALEMIA

38. DETERMININGTHE URGENCY OFTHERAPY
The urgency of treatment of hyperkalemia varies with
• The presence or absence of the symptoms and signs associated
with hyperkalemia,
• The severity of the potassium elevation, and the cause of
hyperkalemia.
Approach to therapeutic urgency is as follows
TREATMENT

41. 3 main approaches to the
treatment of Hyperkalemia

42. 1. Immediate antagonism of the cardiac effects of 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.
• Calcium can be given as either calcium gluconate or calcium chloride.
Calcium chloride contains 3 times the concentration of elemental
calcium compared with calcium gluconate (13.6 versus 4.6 mEq in 10 mL
of a 10 percent solution).
• However, calcium gluconate is generally preferred because calcium
chloride may cause local irritation at the injection site.
• The usual dose of calcium gluconate is 1000 mg (10 mL of a 10 percent
solution) infused over two to three minutes, with constant cardiac
monitoring.The usual dose of calcium chloride is 500 to 1000 mg (5 to
10 mL of a 10 percent solution), also infused over two to three minutes,
with constant cardiac monitoring.

43. • The effect of the infusion starts in 1–3 min and lasts 30–60 min.The
dose of either formulation can be repeated after 5 minutes if the ECG
changes persist or recur.
• Hypercalcemia potentiates the cardiac toxicity of digoxin; hence,
intravenous calcium should be used with extreme caution in patients
taking this medication;
• if judged necessary, 10 mL of 10% calcium gluconate can be added to
100 mL of 5% dextrose in water and infused over 20–30 min to avoid
acute hypercalcemia.
• Concentrated calcium infusions (particularly calcium chloride) are
irritating to veins, and extravasation can cause tissue necrosis. As a
result, a central or deep vein is preferred for administration of calcium
chloride.
• Calcium gluconate can be given peripherally, ideally through a small
needle or catheter in a large vein.
• Calcium should not be given in bicarbonate-containing solutions, which
can lead to the precipitation of calcium carbonate.

44. 2. Rapid reduction in plasma K+ concentration by redistribution into
cells.
Insulin with glucose
• Insulin administration lowers the serum potassium concentration by
driving potassium into the cells, primarily by enhancing the activity of
the Na-K-ATPase pump in skeletal muscle.
• Glucose is usually given with insulin to prevent the development of
hypoglycemia. However, insulin should be given alone if the serum
glucose is ≥250 mg/dL (13.9 mmol/L) and serum glucose should be
measured every hour for 5-6 hrs after the administration of insulin,
given the risk of hypoglycemia.
• One commonly used regimen for administering insulin and glucose is 10
to 20 units of regular insulin in 500 mL of 10 percent dextrose, given
IV over 60 minutes.

45. • Another regimen consists of a bolus injection of 10 units of regular
insulin, followed immediately by 50 mL of 50 percent dextrose (25
g of glucose).This regimen may provide a greater early reduction in
serum potassium since the potassium-lowering effect is greater at
the higher insulin concentrations attained with bolus therapy.
• However, hypoglycemia occurs in up to 75 percent of patients
treated with the bolus regimen, typically approximately one hour
after the infusion.To avoid this complication, recommendation is to
subsequent infusion of 10 percent dextrose at 50 to 75 mL/hour and
close monitoring of blood glucose levels every hour for 5-6 hr.
• The effect of insulin begins in 10 to 20 minutes, peaks at 30 to 60
minutes, and lasts for four to six hours. In almost all patients, the
serum potassium concentration drops by 0.5 to 1.2 mEq/L.
• In particular, although patients with renal failure are resistant to the
glucose-lowering effect of insulin, they are not resistant to the
hypokalemic effect, because Na-K-ATPase activity is still enhanced

46. β2-agonists
• Most commonly albuterol, are effective for the acute management of
hyperkalemia. Albuterol and insulin with glucose have an additive
effect on plasma K+ concentration;
• however, ~20% of patients with end-stage renal disease (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

47. Intravenous bicarbonate
• It 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, but should instead be infused in
an isotonic or hypotonic fluid (e.g., 150 mEqu 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.

48. 3. Removal of potassium.
 The cation exchange resin.
• Sodium polystyrene sulfonate (SPS) “Kayexalate’’
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 administered SPS via enema and/or in patients with reduced
intestinal motility (e.g., in the postoperative state or after treatment
with opioids).

49.  Diuretics, and Dialysis
• 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.
• Hemodialysis is the most effective and reliable method to reduce
plasma K+ concentration. Hemodialysis should be performed in patients
with ESRD or severe renal impairment.
• The amount of K+ removed during hemodialysis depends on the relative
distribution of K+ between ICF and ECF, 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.

50. Reversible causesof impaired renal function associated
hyperkalemia.
• Includes hypovolemia, NSAIDs, urinary tract obstruction, and
inhibitors of the renin-angiotensin- aldosterone system (RAAS),
which can also directly cause hyperkalemia
RX- Removal of offending agent & Hydration
Dietary modification
• It is rare for hyperkalemia to occur exclusively due to excessive intake,
although such cases have been described.

51. • By contrast, the presence of renal disease predisposes to hyperkalemia
in patients consuming potassium.
• In addition to renal impairment, other predisposing factors include
hypoaldosteronism and drugs that inhibit the RAAS can result in
significant hyperkalemia after only modest intake of potassium.
• Such patients should be assessed for their intake of potassium-rich
foods, and counseled to avoid these foods.
• Often, the adoption of a potassium-restricted diet normalizes serum
potassium levels and affords the resumption of RAAS antagonists even
in patients with CKD.

53. Thank you