POTASSIUM DISORDERS

FIRST I will discuss briefly WHAT IS POTASSIUM

PPT 1

-Homeostatic mechanisms maintain plasma K+ concentration between 3.5 and

5.0 mM
-Distributed intracellularly
-Only 2% is extracellular
-Crucially dependent on the total amount of potassium in the body and the
distribution of this potassium between the extracellular and intracellular fluid
compartments

PPT 2

-High intracellular levels is maintained by the Na-K- ATPase pump

IMPORTANCE:
• Excitability of nerves and muscles
• Helps maintain acid-base balance and kidney function
Changes in the exchange and distribution of intra- and extracellular K+ can thus
lead to marked hypo- or hyperkalemia

HYPOKALEMIA

• Extracellular K+ exchanged by intracellular H+ ions to maintain

PH
• Increased hematopoiesis: GM-CSF used to treat neutropenia and B12 and
folic acid to treat megaloblastic anemia may cause sharp rise in cell
production and increased K+ entry into cell causes hypokalemia

• plasma K+ concentration of <3.5 mM

• occurs in up to 20% of hospitalized patients
• associated with a tenfold increase in in-hospital mortality, due to adverse
effects on cardiac rhythm, blood pressure, and cardiovascular morbidity
• Long-standing hypokalemia may predispose to acute kidney injury and lead
to ESRD
There are 3 causes that would result to hypokalemia and these are the following;
Decrease Intake, Redistribution Into Cell and Increased Loss

• External potassium balance is determined by the rate of potassium intake

(normally 100 mEq/day) and rate of urinary (normally 90 mEq/day) and
fecal excretion (normally 10 mEq/day). The distribution of potassium in
muscles, bone, liver and red blood cells (RBC) and ECF has a direct effect on
internal potassium balance
Metabolic Alkalosis
• Extracellular K+ exchanged by intracellular H+ ions to maintain
PH
• B. HORMONAL
• 1. INSULIN
• -Exogenous insulin glucose infusion increases potassium enrty
into skeletal and hepatic cells by promoting Na-K-Atpase activity.
• -This effect is more prominent when administered in settings of
DKA or nonketotic hyperglycemia
• 2. Increased β -adrenergic sympathetic activity:
• -Alterations in the activity of the endogenous sympathetic nervous
system can cause hypokalemia in several settings, including alcohol
withdrawal, hyperthyroidism, acute myocardial infarction, and severe head
injury
• 3. β -Adrenergic agonists and α-Adrenergic antagonists
• -β2 agonists, including both bronchodilators and tocolytics
(ritodrine), are powerful activators of cellular K+ uptake;
• - “hidden” sympathomimetics, such as pseudoephedrine and
ephedrine in cough syrup or dieting agents, may also cause
unexpected hypokalemia
• 5. Thyrotoxic periodic paralysis
• -Excess thyroid hormone increase N—K- ATPase activity,
increased B- adrenergic response and predisposes to paralytic attacks with
profound hypokalemia ranging between 1.1-2.5 mEq/L
• -Typically present with weakness of the extremities and limb
girdles, with paralytic episodes that occur most frequently between 1
and 6 a.m.
• -High-dose propranolol (3 mg/kg) rapidly reverses the
associated hypokalemia, hypophosphatemia, and paralysis.
 • 6. Downstream stimulation of Na+/K+-ATPase:
• xanthine dependent activation of cAMP-dependent signaling,
downstream of the β2 receptor, can lead to hypokalemia, usually in
the setting of overdose (theophylline) or marked over ingestion (dietary
caffeine)
• Increased hematopoiesis: GM-CSF used to treat neutropenia and B12 and
folic acid to treat megaloblastic anemia may cause sharp rise in cell
production and increased K+ entry into cell causes hypokalemia
•
NON-RENAL
• Sweating in extremes of physical exertion
• Gastric losses (vomiting, ryles aspiration)- ensuing hypochloremic alkalosis
results in persistent kaluresis due to secondary hyperaldosteronism and
bicarbonaturea
• Diarrhea is a known cause of K+ loss and may present with acute
complications like myopathy and flaccid paralysis.
• Non anion gap acidosis with negative urinary anion gap suggests diarrhoea
as a cause

I would first discuss the Decrease Intake – Next silde please

Both Starvation and Clay Ingestion would result to hypokalemia since the
Decrease intake

REDISTRIBUTION

Potassium plays a key role in maintaining normal cell function. K+ is the main intracellular cation
and almost all cells have the pump called ‘Na+-K+-ATPase’, which pumps sodium (Na+) out of
the cell and K+ into the cell leading to a K+ gradient across the cell membrane (K+ in > K+ out),
which is partially responsible for maintaining the potential difference across membrane.

A. ACID BASE
1. Metabolic Alkalosis
B. HORMONAL
1. Insulin
2. Increased β -adrenergic sympathetic activity:
post–myocardial 2 infarction, head injury
3.β -Adrenergic agonists
bronchodilators, tocolytics 2
4. α-Adrenergic antagonists
5. Thyrotoxic periodic paralysis
6. Downstream stimulation of Na+/K+-ATPase:
theophylline, caffeine
• Redistribution Into Cell
C. Anabolic state
1. Vitamin B12 or folic acid administration (red blood cell production)
2. Granulocyte-macrophage colony-stimulating factor (white blood
cell production)
3.Total parenteral nutrition
D. Other
1. Pseudohypokalemia
2. Hypothermia
3. Familial hypokalemic periodic paralysis
4. Barium toxicity: systemic inhibition of “leak” K+ channels
Causes of Hypokalemia
Causes of Hypokalemia
Causes of Hypokalemia
CLINICAL FEATURES
CLINICAL FEATURES
CCLINICAL FEATURES
 CLINICAL FEATURES
•
CLINICAL FEATURES
Electrocardiographic changes in hypokalemia include
• broad flat T waves
• ST depression
• QT prolongation
most marked when serum K+ is <2.7 mmol/L
• DIAGNOSTIC APPROACH
• DIAGNOSTIC APPROACH
HISTORY
- medications (e.g., laxatives, diuretics, antibiotics), diet and dietary habits
(e.g., licorice), and/or symptoms that suggest a particular cause (e.g., periodic
weakness, diarrhea)
The underlying cause of hypokalemia is usually apparent after obtaining a
detailed medical history and physical examination (24). In order to evaluate the severity
of hypokalemia and to initiate an effective treatment, assessment of serum and urinary
potassium levels is needed. Depending on the above findings, tests and imaging of the
endocrine glands are appropriate, but they should not be first-line tests unless the clinical
index of suspicion for such a disorder is high.

PHYSICAL EXAMINATION
-blood pressure, volume status, and signs suggestive of specific hypokalemic
disorders, e.g., hyperthyroidism and Cushing’s syndrome
• DIAGNOSTIC APPROACH
• A basic biochemical laboratory panel (including serum sodium, potassium, glucose,
chloride, bicarbonate, BUN and creatinine) is the core of screening in patients with
hypokalemia. Urine electrolytes (potassium and chloride) in spot urine are useful in
differentiating renal from non-renal causes of hypokalemia. An arterial blood gas (ABG)
analysis should be performed to detect metabolic acidosis or alkalosis when the
underlying cause is not apparent from the history. As the difference between arterial and
vein blood samples, regarding the potassium levels, is clinically not significant,
measurement of potassium in vein blood sample is not contraindicated in the emergency
department. Further urinalysis and urine pH measurement should follow to assess for the
presence of renal tubular acidosis. Serum magnesium, calcium and/or phosphorus levels
are important to exclude associated electrolyte abnormalities, especially if alcoholism is
suspected. Urinary calcium excretion is very critical to exclude Bartter syndrome. We
should also measure serum digoxin level if the patient is on digitalis. In cases of high
clinical index of suspicion for a disorder, a drug screen in urine and/or serum for
 diuretics, amphetamines and other sympathomimetic stimulants should be conducted.
Assessment of TSH levels is required in cases of tachycardia or clinical suspicion of
hypokalemic periodic paralysis (25).
• In general, there are two major components of the diagnostic evaluation: (a) assessment
of urinary potassium excretion in order to distinguish renal potassium losses (e.g.,
diuretic therapy, primary aldosteronism) from other causes of hypokalemia (e.g.,
gastrointestinal losses, transcellular potassium shifts) and (b) assessment of acid–base
status, since some causes of hypokalemia are associated with metabolic alkalosis or
metabolic acidosis. We present a diagnostic algorithm for the assessment of hypokalemia

Laboratory Test
• D. Management
1. Goal of Therapy
·  Prevent life-threatening and/or chronic consequences
·  Replace the potassium deficit
·  Correct the underlying cause and/or mitigate future
hypokalemia
2. Correcting the Potassium Deficit
·  Urgency of therapy depends on severity of hypokalemia,
associated clinical factors & rate of decline
·  Oral replacement is the mainstay of therapy
·  Concomitant magnesium deficiency should always be corrected
• Intravenous administration
• Limited to patients unable to use the enteral route or with severe
complications (e.g., paralysis, arrhythmia)
• Intravenous K+-Cl– should always be administered in saline solutions, rather
than dextrose

- Dextrose-induced increase in insulin can acutely exacerbate

hypokalemia
• The peripheral intravenous dose is usually 20–40 mmol of K+-Cl– per liter

-higher concentrations can cause localized pain from chemical

phlebitis, irritation, and sclerosis.
• Intravenous administration
If hypokalemia is severe (<2.5 mmol/L) and/or critically symptomatic,
 -intravenous K+-Cl– can be administered through a central vein with
cardiac monitoring in an intensive care setting, at rates of 10–20 mmol/h;
higher rates should be reserved for acutely life- threatening complications
The absolute amount of administered K+ should be restricted (e.g.,
20 mmol in 100 mL of saline solution) to prevent inadvertent infusion of a
large dose
Femoral veins are preferable, because infusion through internal jugular or
subclavian central lines can acutely increase the local concentration of K+ and
affect cardiac conduction

• Redistribution Into Cell

D. Other
1. Pseudohypokalemia
-Delay in sample analysis may cause hypokalemia due to time
dependent intracellular shift of K+
-Rarely profound leukocytosis due to acute leukemia may cause
artifactual hypokalemia without any clinical or ECG manifestations.
-This can be avoided by analysing sample immediately after
venipuncture

2. Hypothermia
-Results in a drive of K+ into cells which is reversible on rewarming

• Redistribution Into Cell

D. Other
3. Familial hypokalemic periodic paralysis
Similar episodes of hypokalemic weakness (TPP) in the absence
of thyroid abnormalities occur in familial hypokalemic periodic paralysis
Caused by missense mutations of voltage sensor domains within
the α1 subunit of L-type calcium channels or the skeletal Na+ channel; these
mutations generate an abnormal gating pore current activated by
hyperpolarization

• Redistribution Into Cell

D. Other
 4. Barium toxicity: systemic inhibition of “leak” K+ channels
• Barium is apotent inhibitor of passive K+
efflux channels
• Treatment with K+ repletion serves to both
rising serum K+ and to replace barium from
efflux channels
Causes of Hypokalemia
Causes of Hypokalemia
Causes of Hypokalemia
• RENAL
Diuretics:
Diuretics are an important cause of hypokalemia by increasing distal delivery of
Na and increasing distal flow.
Thiazides cause more hypokalemia than loop diuretics despite their lower
natriuretic effect due to their differential effect on calcium excrtetion.
Hypercalciurea caused by loop diuretics increases luminal calcium which inturn
inhibitd ENaC in the principal cells.
• Non-reabsorbable anions:
• Nonreabsorbable anions in the distal nephron like penicillin, nafacillin,
dicloxacillin,ticarcillin,oxacillin,carbencilli n and other anions like
bicarbonate increase obligatory K+ excretion and thereby kaliuresis. ž
• K+ excretion Increases to balance negative charge of these anions.
Tubular toxins:
Several tuular toxins can cause combined K+ and Magnesium wasting that
can masquerade as Bartter’s syndrome. ž Eg:gentamycin,amphoterecin,
foscarnet, cisplatin, ifosfamide. ž Hpokalemia is refractory to K+ repletion unless
concomitant Mg supplementation is given.
CLINICAL FEATURES
CLINICAL FEATURES
CCLINICAL FEATURES
CLINICAL FEATURES
•
CLINICAL FEATURES
Electrocardiographic changes in hypokalemia include
• broad flat T waves
• ST depression
 • QT prolongation
most marked when serum K+ is <2.7 mmol/L
• DIAGNOSTIC APPROACH
• DIAGNOSTIC APPROACH
HISTORY
- medications (e.g., laxatives, diuretics, antibiotics), diet and dietary habits
(e.g., licorice), and/or symptoms that suggest a particular cause (e.g., periodic
weakness, diarrhea)
PHYSICAL EXAMINATION
-blood pressure, volume status, and signs suggestive of specific
hypokalemic disorders, e.g., hyperthyroidism and Cushing’s syndrome