MEDICINE 2 – [NEPHRO]: GENERAL LECTURE
09 SEPT 21
Dr. Romina Jasmin Laguesma-Navarro
TABLE OF CONTENTS
I. POTASSIUM PHYSIOLOGY .................................................. 1
A. GENERALITIES ................................................................ 1
B. KIDNEYS IN POTASSIUM HOMEOSTASIS...................... 1
II. HYPOKALEMIA ..................................................................... 2
A. ETIOLOGY ............................................................................. 2
C. CLINICAL FEATURES ........................................................... 4
D. DIAGNOSTIC APPROACH .................................................... 4
E. TREATMENT .......................................................................... 5
III. HYPERKALEMIA ................................................................... 6
A. ETIOLOGY ............................................................................. 6
B. CLINICAL FEATURES ............................................................ 7
C. DIAGNOSTIC APPROACH .................................................... 8
D. TREATMENT ......................................................................... 8
CASE 1 ............................................................................................ 9
CASE 2 .......................................................................................... 10
Q & A ……………………………………………………………………..11
REFERENCES .............................................................................. 12
MUST KNOW BOOK PREVIOUS TRANS
   → K+ reabsorption in the thick ascending limb of Henle is
I. POTASSIUM PHYSIOLOGY
A. GENERALITIES
● Normal K+ concentration: 3.5-5.0 mEq/L U
→ This is maintained despite marked variation in the dietary
potassium intake.
● 98% of total body K+ is intracellular, mainly in muscles
→ Large intracellular pool buffers extracellular K+
■ Plays a crucial role in the regulation of plasma K+
concentration
■ Changes in the exchange and distribution of intracellular
and extracellular potassium can lead to marked
hypokalemia or hyperkalemia
→ Massive necrosis with release of tissue K+ may cause
severe hyperkalemia
■ Particularly in the setting of AKI and reduced K+ excretion
● In a healthy individual, the entire daily intake of potassium
intake is excreted at steady state
→ Excretion: urine (~90%) and stool (10%)
→ Kidneys play a dominant role in potassium homeostasis
Figure 1. Potassium homeostasis. Lifted from 2022 trans. Serum (extracellular)
K+ is maintained by the absorption/excretion/reabsorption of the renal
(primarily) and GI systems. The massive intracellular K+ stores buffers
fluctuations in the extracellular pool.
A-TG14 | CABILLAR | CACHUELA, CALIMAG, CAMPOS, CANIVEL, CANLAS
AY 21-22
23 NOV 21
B. KIDNEYS IN POTASSIUM HOMEOSTASIS
● Changes in total body K+ are mediated primarily by the kidneys
→ Reabsorbs filtered K+ in hypokalemic/potassium-deficient
states
→ Secretes filtered K+ in hyperkalemic/potassium-replete
states
● Although K+ is transported along the entire nephron, it is the
principal cells of the connecting segment (CNT) and cortical
duct (cortical CD) that plays a dominant role in renal K+
secretion
● Alpha intercalated cells of the outer medullary cortical duct
function in renal tubular reabsorption of filtered K+ in
potassium-deficient states
● Refer to Figure 2:
→ Approximately 90% of filtered K+ is reabsorbed in the
proximal tubule and the loop of Henle, such that <10% of
the filtered load is delivered to the early distal tubule.
→ Proximal K+ transport appears to passively follow that of Na +
and water.
mediated by the Na-K-Cl carrier in the luminal membrane.
→ K+ is secreted along the connecting segment, the principal
cells, and cortical & outer medullary collecting tubule.
→ Secretions in these segments may vary according to the
physiologic needs or conditions as follows:
■ High potassium intake
■ Increased aldosterone and ADH
■ Increased tubular flow
■ Alkalosis
→ Potassium reabsorption happens in the intercalated cells in
the cortical and outer medullary collecting tubules.
■ This is mediated by the hydrogen potassium ATPase
pumps, and the activity of these pumps is increased with
potassium depletion.
→ Net reabsorption occurs in response to K+ depletion, primarily
within the medullary collecting duct.
Figure 2. K+ transport along the nephron. Lifted from Potassium disorders
lecture.
Proximal Nephron
● Almost all of the filtered K+ are reabsorbed in the PCT and the
loop of Henle (90%); <10% of the filtered load is delivered to the
early distal tubule
→ PCT: K+ transport passively follows transport of Na + and water
→ Loop of Henle: K+ transport is mediated by NKCC2
Distal Nephron
Principal Cells
● Renal potassium secretion in the principal cells of the cortical
collecting duct
● Connecting segment (CNT) and cortical collecting duct (CD)
● Mediates potassium secretion 
Page 1 of 13
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021) Page 2 of 13

● Apical Na+ entry via ENaC (amiloride-sensitive epithelium

sodium channel) generates a lumen-negative potential
difference, driving passive K+ secretion via apical K + channels
(ROMK and BK)
● Two major potassium channels that mediate distal tubular K+
secretion: 
→ Secretory ROMK (renal outer medullary K+ channel;
Kir1.1 or KcnJ1)
■ Mediates bulk of constitutive K+ secretion
→ Flow-sensitive BK (“big potassium”) or maxi-K K+
channel
■ Increased distal flow rate and/or genetic absence of
ROMK activates K+ secretion via this channel
● Increased distal flow enhances Na+ delivery and reabsorption of
K+ in the cortical collecting duct via the ROMK and BK
channels Figure 4. Aldosterone action on the distal nephron.
→ Basolateral Na+/K+-ATPase transports Na+ out of the cell, Alpha-intercalated cells
resulting in entry of K+ intracellularly which are then secreted ● Renal potassium reabsorption in the alpha intercalated cells of
● Refer to Figure 3 the outer medullary duct
→ (Encircled in blue) Na+ entry through the epithelium sodium
● Outer medullary collecting duct
channel (ENaC) generates a lumen-negative potential
difference that favors the movement of K+ from the cells into ● Mediates potassium reabsorption
the lumen, through the renal outer medullary K+ channel ● Electrolyte transporter
(ROMK) and/or flow dependent BK channel (Maxi-K) → Luminal H+/K+ ATPase pump
→ (Encircled in red) The subsequent transport of Na+ out of the → Basolateral K+ channel
cell, by the Na+/K+-ATPase pumps in the basolateral ● Under potassium-restricted conditions
membrane results in the new entry of K+ into the cells, → Enhanced H+/K+ ATPase activity
thereby producing more K+ for continued secretion → K+ is reabsorbed via apical H+/K+-ATPase and exits the
intercalated cells via a basolateral K+ channel (thus achieves
the transepithelial transport of K+)

Figure 5. Potassium secretion in the alpha-intercalated cells.

II. HYPOKALEMIA
● Plasma K+ concentration of <3.5 mEq/L
● Occurs in up to 20% of hospitalized patients
● Associated with a tenfold increase in-hospital mortality
→ Due to adverse effects on cardiac rhythm, blood pressure, and
cardiovascular morbidity
● Pseudohypokalemia (spurious hypokalemia )
→ Due to in vitro cellular uptake of K+ after venipuncture
■ Specimen left standing for hours at warm temperatures
before processing
■ With the same pathophysiology, it may be seen in acute
Figure 3. Secretion of potassium.
leukemia, due to profound leukocytosis
● Aldosterone (Refer to Figure 4)  A. ETIOLOGY
→ Luminal membrane: increases the number of open ENaC Decreased Intake
and K+ channels
→ Basolateral membrane: enhances activity of Na+/K+-ATPase ● During starvation
pumps → Renal response to potassium depletion is sufficiently
effective, that a low potassium diet will not lead to significant
potassium losses unless intake is severely limited
● Clay Ingestion
→ Chronic clay ingestion is a common practice in some rural
areas in southeastern USA
→ The clay appears to bind dietary potassium
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021)
Redistribution Into Cells
● Metabolic Alkalosis
→ Especially in the setting of dehydration, increased
aldosterone secretion causes increased H+/K+-ATPase
pumps and their corresponding activity.
■ This results in increased potassium secretion in the
collecting ducts, specifically in the principal cells
→ Aldosterone increases ENaC activity, amplifying the driving
force for K+ secretion across the luminal membrane of
principal cells (Harrison’s 20th Edition)
● β2-adrenergic agonists activity and insulin (post MI)
→ Both promote cellular uptake of K+ by skeletal muscle and
the liver
→ Increased sympathetic activity: drugs
pseudoephedrine, ephedrine, bronchodilators, tocolytics),
alcohol withdrawal, hyperthyroidism, acute MI, severe head
injury)
→ Seen in post-MI
→ Reflected by stress-induced epinephrine release, thereby
promoting K+ uptake into the cells
● Methylxanthines 
→ Activate cAMP-dependent β2 receptor signaling downstream
→ Downstream stimulation of Na+/K+-ATPase:
Theophylline overdose, marked over ingestion of caffeine
● Thyrotoxicosis
→ General mechanisms
■ Increased sensitivity to catecholamines
■ Thyroid hormones increase Na+/K+-ATPase, driving
intracellular K+ transport (K+ is driven into the cells)
→ Thyrotoxic periodic paralysis (TPP)
■ Higher sodium pump activity
■ Genetic variation in Kir 2.6 (muscle-specific thyroid
hormone-responsive K+ channel)
■ More common in Asians and Hispanics 
● Theophylline & Caffeine
→ Downstream stimulation of Na+/K+ ATPase upon intake
● Anabolic states
→ Ex. Increased hematopoietic cell production by the bone
marrow
■ Hypokalemia is associated with potassium uptake by
new cells
■ This can be seen in patients with megaloblastic anemia
treated with vitamin B12 or folic acid
■ Neutropenia corrected by GCSF administration
− Marked hypokalemia can be induced by granulocyte
colony-stimulating factor (GCSF) to correct
neutropenia
■ RBCs and WBCs increase intracellular sites, hence the
redistribution of K+ into the cells
→ Total parenteral nutrition causing refeeding syndrome
■ Specially in cases in patients placed on NPO for >1 week
and then the TPN has started
■ Increase in glucose load evokes insulin release
increasing cellular uptake of glucose, K+, PO4, and Mg2+
● Other causes
→ Pseudohypokalemia
→ Hypothermia: multiple mechanisms
→ Barium toxicity: systemic inhibition of “leak” K+ channel
→ Familial hypokalemic periodic paralysis
■ Mutations in voltage sensor domains within the α1 subunit
of L-type Ca2+ channels or skeletal Na+ channels
Nonrenal Potassium Loss
● Gastrointestinal loss
→ Secondary to increased intestinal secretion of K + due to
upregulation of colonic BK channels
■ Seen in diarrhea, intestinal fistula, chronic laxative
abuse, celiac disease, ileostomy, villous adenomas, IBD,
Ogilvie’s syndrome, VIPomas
→ Vomiting and nasogastric suctioning
■ Hypochloremic alkalosis cause kaliuresis due to secondary
hyperaldosteronism and bicarbonaturia (renal mechanism)
Page 3 of 13
→ Integumentary loss
■ Cutaneous loss of K+ sufficient to cause hypokalemia is
uncommon but may occur during intense exercise in a hot,
humid environment
Renal Potassium Loss
● Increased distal flow and Na+ delivery
→ Diuretics: thiazides > loop diuretics
■ Thiazides: increased Na+ delivery and hypocalciuria
■ Loop diuretics: increased Na+ delivery and hypercalciuria
− Hypercalciuria inhibits ENaC in principal cells,
attenuating the lumen-negative potential difference
→ Osmotic diuresis
→ Salt-wasting nephropathies
(e.g.
● Increased secretion of potassium
→ Glucocorticoid excess
■ Cortisol has mineralocorticoid activity
■ Ex. Cushing’s disease, ectopic ACTH production, etc.
● Mineralocorticoid excess
→ Secondary hyperaldosteronism: renal artery stenosis
→ Primary hyperaldosteronism
■ Genetic
− Congenital adrenal hyperplasia
− Familial hyperaldosteronism (types I-III)
■ Acquired
− Conn’s adenoma
− Primary or unilateral adrenal hyperplasia
− Idiopathic hyperaldosteronism (bilateral hyperplasia)
− Adrenal carcinoma
■ Syndrome of apparent mineralocorticoid excess
(SAME)
− Recessive loss-of-function mutations in 11βHSD-2 gene
− 11β-hydroxysteroid dehydrogenase-2: inactivates
cortisol in the distal nephron, inhibiting its
mineralocorticoid activity
− Licorice: glycyrrhetinic acid which inhibits 11βHSD-2
■ Liddle’s syndrome
− Autosomal dominant gain-in-function mutation of ENaC
leading to increased excretion of potassium
→ Hereditary hypokalemic alkalosis
■ Bartter syndrome: NKCC2 mutations; hypercalciuria
− Loss of Na+, K+, and Cl- transport in the TALH
■ Gitelman’s syndrome: NCC mutations; hypocalciuria
− Loss of Na+ and Cl- transport in the DCT
→ Increased distal delivery of nonreabsorbed anions
■ Vomiting, nasogastric tube, proximal renal tubular
acidosis
− Due to increased levels of bicarbonate, i.e.
bicarbonaturia)
■ Diabetic ketoacidosis
− Due to increased Beta-Hydroxybutyrate
■ Glue sniffing or toluene abuse
− Due to increased Hippurate (non-reabsorbable ion)
■ Penicillin derivatives (when taken in high doses)
− Ex. Penicillin, Nafcillin, Dicloxacillin, Ticarcillin, Oxacillin,
carbenicillin
→ Nephrotoxins: aminoglycosides, amphotericin, foscarnet,
etc.
● Magnesium deficiency
→ Treatment-resistant hypokalemia 
→ Mechanisms
■ Inhibitory effect on muscles
■ Inhibits muscle Na+/K+-ATPase activity, hence reduced
cellular K+ uptake (K+ influx into the potassium cells) and
causing a secondary kaliuresis
■ Reduced magnesium-dependent, intracellular blockade of
K+ efflux via ROMK of principal cells: exaggerated K+
secretion by the distal nephron
→ Note that hypomagnesemia is also commonly concomitant
with hypokalemia in many disorders of the distal nephron
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021) Page 4 of 13

■ Correction of potassium levels will not be achieved if the Skeletal and Smooth Muscle Effects
Magnesium deficiency will not be replaced or replenished ● Muscle weakness and paralysis
first  → Due to hyperpolarization of skeletal muscle, impairing
depolarization
 | MUST KNOW → Muscle weakness begins at plasma K+ <2.5 mEq/L
● Hypokalemia due to renal losses occurs when: → Lower extremities are commonly most involved first,
→ There is increased distal delivery of Na+ and distal particularly the quadriceps femoris
flow which will stimulate K+ secretion (e.g., ● Skeletal myopathy (K+ <2.5 mEq/L)
diuretics) → Predisposes to rhabdomyolysis
● Expected findings on DTR: hyporeflexia
→ Aldosterone increases ENaC activity
● Intestinal ileus
■ Increasing the number of open sodium and
→ Paralytic effects on intestinal smooth muscle
potassium channels in the luminal membrane → Abdominal distention, nausea, vomiting, constipation
■ Enhances the activity of the Na+/K+-ATPase
Renal Complications
pump in the basolateral membrane further
contributing to the secretion of potassium into ● Tubular Dysfunction
the lumen → Na+, Cl-, HCO3- retention (contribute to metabolic alkalosis)
→ Polyuria, phosphaturia, hypocitraturia, and an activation
of renal ammoniagenesis
→ Bicarbonate retention which can contribute to metabolic
alkalosis
→ Hypokalemic polyuria: due to a combination of central
polydipsia and AVP-resistant renal concentrating defect
→ Structural changes
■ Vacuolizing injury specific to proximal tubular cells
■ Interstitial nephritis
■ Renal cysts
● Renal Failure
→ Predisposes to AKI and can lead to ESRD in patients with
chronic hypokalemia due to eating disorders and/or laxative
abuse
D. DIAGNOSTIC APPROACH
C. CLINICAL FEATURES
● History
Cardiovascular Complications → Medications: laxatives, diuretics, antibiotics
● One of the clinical presentation of hypokalemia → Dietary habits: licorice consumption
● Major risk factor for ventricular and atrial arrhythmias → Particular symptoms: periodic weakness, diarrhea
→ Directly enhances automaticity ● Physical Examination
→ Delays ventricular repolarization → Blood pressure and volume status
● Patients who are hypokalemic are predisposed to digoxin → Signs suggestive of hypokalemic disorders
toxicity ■ Hyperthyroidism
→ Reduced competition between K+ and digoxin for shared ■ Cushing’s syndrome
binding sites on cardiac Na+/K+-ATPase subunits ● Laboratory evaluation
● Electrocardiographic changes (marked at serum K+ <2.7 → Blood tests: CBC, electrolytes, BUN, CREA, serum osmolality,
mmol/L) Mg2+, Ca2+
→ Broad, flat T waves → Urine studies: Urinary pH, osmolality, creatinine, electrolytes
→ ST depression → Others: Urinary Ca2+, thyroid function tests, PRA and
→ U waves aldosterone levels
→ QT prolongation → Assessment of renal potassium excretion will help determine
● Implicated in progression of hypertension, heart failure, stroke whether the hypokalemia is due to renal or extrarenal causes
→ K+ restriction in hypertensives may induce NaCl retention and ● Refer to Appendix for Diagnostic Approach to Hypokalemia
aggravate hypertension, and may lead to progression of heart Transtubular Potassium Gradient (TTKG)
failure as well as stroke
● Index of tubular fluid K+ concentration at end of the cortical
collecting tubule
→ Ratio of K+ concentration in the lumen of the CCD to than in
peritubular capillaries (plasma)
● Formula: (Posmol x Upotassium)/(Ppotassium x Uosmol)
● Expected values
→ <3: hypokalemia
→ >7-8: hyperkalemia
Specific Associations 
● Non-anion gap acidosis
→ Distal, hypokalemic renal tubular acidosis or diarrhea
→ Differentiated by urinary anion gap
Figure 6. Electrocardiographic changes in hypokalemia.
● Renal K+ excretion of <15 mmol/L in 24-hour urine
→ Extrarenal cause of hypokalemia
● Urinary K+-to-creatinine ratio >13 mmol/g (>1.5 mmol/mmol)
→ Excessive renal K+ excretion
● Urine Cl- is decreased
→ Nonreabsorbable anions (e.g. antibiotics, HCO -)
● Plasma aldosterone:plasma renin activity ratio (PRA) >50
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021)
→ Suggestive of hyperaldosteronism
→ Further testing: adrenal vein sampling, genetic testing
● Response to diuretics
→ Differentiation of Liddle’s syndrome and SAME, both of which
cause hypokalemia, hypertension, aldosterone suppression
→ Liddle’s syndrome: responds to amiloride
→ SAME: responds to spironolactone
→ Chronic hypokalemic alkalosis
→ Differentiated based on urinary electrolyte pattern
→ Vomiting due to bulimia: urinary Cl- <10 mmol/L
■ Gitelman’s syndrome: elevated urine Na+, K+, and Cl-
■ Diuretic abuse: elevated urine electrolytes, but to a lesser
extent and with greater variability
Diagnostic Approach to Hypokalemia
Figure 7. Algorithm for a patient presenting with hypokalemia.
Referring to Figure 7:
● When a patient clinically presents with hypokalemia and if indeed
hypokalemic:
→ Check for ECG changes or has arrhythmia because this is an
emergency
→ If you see one, automatically treat the patient
● For pseudo hypokalemic patients
→ No work up is needed
● More stable patient
→ Continue with your history, PE, and other basic laboratory
tests
● Clinical or clear evidence of low K+ intake
→ Treat the patient accordingly and then reevaluate
● Evidence of transcellular shifting
→ Treat the patient accordingly, and then evaluate
● No clear evidence of low intake and transcellular shift
→ Requests for urine potassium
■ 24-hour urine potassium OR
■ Urinary potassium-creatinine ratio
Figure 8. Urine Potassium.
Referring to Figure 8:
● If the 24-hour urine K+ is <15 mmol/day OR <15mmol/g Cr
(urinary potassium-to-creatinine ratio)
→ Think of extrarenal loss or remote renal loss
→ Request for ABG to check for Acid Base Status
■ Metabolic acidosis: check for GI K+ loss
■ Normal: check if it’s because of profuse sweating
■ Metabolic alkalosis: check for remote diuretic use, remote
vomiting or stomach drainage, or even profuse sweating
● If the 24-hour urine K+ urine K+ is >15 mmol/day OR
>15mmol/g Cr (urinary potassium-to-crea ratio)
→ Think of renal loss
Page 5 of 13
→ Compute for the TTKG
■ <2: think of increased tubular flow
■ Seen in osmotic diuresis
■ >4: there is increased distal potassium excretion
→ Check for the volume status and BP of the patient
Figure 9. Blood Pressure/ Volume Status. *RTA: Renal
tubular acidosis
Refer to Figure 9:
● High Blood Pressure
→ Check the aldosterone
■ High: check the renin then check the succeeding steps in
the algorithm
■ Low: check cortisol then check the succeeding steps in the
algorithm
● Low or normal blood pressure
→ Assess the acid base status
■ Normal or variable: think of non-reabsorbable anions other
than HCO3- (e.g., Hippurate seen in glue sniffing and use
of Penicillin)
■ Metabolic Acidosis: think of proximal RTA, distal RTA,
DKA, Amphotericin B, acetazolamide
■ Metabolic Alkalosis: request for Urine Cl-, Ca+2, creatinine
ratio and follow the algorithm as seen above
E. TREATMENT
Generalities
● Goals of Therapy
→ Prevent life-threatening and/or serious chronic consequences
like arrythmia
→ Replace the K+ deficit
→ Correct underlying cause and/or mitigate future hypokalemia
● Continuous cardiac telemetry during correction
→ For patients with prolonged QT interval and/or other risk
factors for arrhythmia
■ Hook the patient to a cardiac monitor during correction and
observe for ECG changes
● Urgent but cautious K+ replacement in patients with severe
redistributive hypokalemia
→ Watch out for risk of rebound hyperkalemia following acute
resolution of the underlying cause
→ Monitor frequently the potassium levels
● Minimization of K+ lost
→ Reduce the dose of non-potassium-sparing diuretics
→ Restrict sodium intake
→ Use appropriate combinations of non-potassium-sparing and
potassium-sparing medications (e.g. loop diuretics + ACEI)
● Indications for urgent but cautious K+ replacement
→ Severe redistributive hypokalemia (<2.5 mM)
→ Patients with serious complications
→ Risk of rebound hyperkalemia following acute resolution of the
underlying cause
● Give high-dose propranolol (3 mg/kg) 
→ If excessive sympathetic activity plays a dominant role
■ TPP, theophylline overdose, acute head injury
→ Nonspecific β-blocker corrects hypokalemia without the risk of
rebound hyperkalemia
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021)
Oral Potassium Replacement
● Oral potassium chloride (KCl) is the mainstay of therapy for
treatment of hypokalemia 
● K+ phosphate: for hypokalemia + hypophosphatemia
● K+ bicarbonate/ K+ citrate: for hypokalemia + metabolic acidosis
● Estimation of total K+ deficit (without abnormal K+ redistribution)
→ Serum K+ drops by ~0.27 mmol/L for every 100 mmol
reduction in total-body stores
■ Loss of 400-800 mmol of total body K+ results in a
reduction in serum K+ by ~2.0 mmol/L
● Estimation of the rate of correction
→ Consider renal function, medications, comorbid conditions
→ K+ deficit must be replaced cautiously over 24-48 hours
■ Due to delay in redistribution to intracellular compartments
■ Frequently monitor plasma K+ to avoid transient
overcorrection and transient hyperkalemia
● Concomitant Mg2+ deficiency should always be corrected
with oral or intravenous repletion 
→ If the cause of the hypokalemia is magnesium deficiency,
correct first the magnesium or concomitant correction of
hypomagnesemia with the correction of hypokalemia
→ Hypomagnesemic patients are refractory to K+ therapy alone
Intravenous Potassium Replacement (IV KCl Correction)
● Indications 
→ Patients unable to use the enteral route
→ Severe complications (e.g., paralysis, arrhythmia)
● Administer intravenous KCl only in saline solutions 
→ DO NOT use dextrose solutions because dextrose-induced
increase in insulin can acutely exacerbate hypokalemia
● Peripheral vein access: 20-40 mmol of KCl per liter IVF
→ Higher concentrations can cause localized pain from chemical
phlebitis, irritation, and sclerosis
● Central vein access: 10-20 mmol/h (higher dose)
→ Indications 
■ Severe hypokalemia (<2.5 mmol/L)
■ Critically symptomatic patients
→ Other considerations
■ Administered with cardiac monitoring in an ICU setting
because it can be given at high dose rates (e.g., 10-20
mmol/hour)
■ Higher rates should be reserved only for acutely life-
threatening complications
■ The absolute amount of K+ should be restricted (e.g., 20
mmol in 100 mL of saline solution via drip) to prevent
inadvertent infusion of a large dose
→ Femoral veins are preferable
■ The central line that empties directly into the right atrium is
discouraged
■ Infusion through the IJV or subclavian central lines can
acutely increase the local concentration of K+ and affect
cardiac conduction
III. HYPERKALEMIA
● K+ phosphate: for hypokalemia + hypophosphatemia
● Plasma K+ concentration of >5.5 mEq/L U
→ Severe hyperkalemia (>6.0 mEq/L) increases risk of mortality
● Causes of hyperkalemia
→ Redistribution and reduced tissue uptake
→ Decrease in renal K+ excretion (most common)
→ Excessive intake of K+ is rare but seen in:
■ Diabetes with hyporeninemic hypoaldosteronism
■ CKD
→ Drugs affecting the RAAS
● Pseudohyperkalemia (or factitious hyperkalemia)
→ Artifactual increase in serum K+ due to release of K+
during or after venipuncture
→ Settings:
■ Excessive muscle activity during venipuncture (e.g. fist
clenching)
Page 6 of 13
■ Marked increase in cellular elements (e.g.
thrombocytosis, leukocytosis, and/or erythrocytosis) with in
vitro K+ efflux
■ Acute anxiety during venipuncture with respiratory
alkalosis and redistributive hyperkalemia
■ Cooling of blood sample following venipuncture due to
reduced cellular uptake
■ Multiple genetic subtypes of hereditary
pseudohyperkalemia caused by increases in passive K+
permeability of the RBCs
− SLC4A1 gene mutations; multiple genetic subtypes
− AE1 anion exchanger-mediated K+ leak from RBCs
A. ETIOLOGY
Redistribution and Reduced Tissue Uptake
● Metabolic Acidosis 
→ Non-anion gap metabolic acidosis; respiratory acidosis (to a
lesser extent); does not occur with lactic acidosis, ketoacidosis
→ Compensatory H+ cellular uptake with K+ efflux, which
maintains electroneutrality/maintain extracellular pH
● Hyperosmolality
→ “Solvent drag” effect: pull water and K+ out from the cell hence
shifting K+ to the ECF
→ Radiocontrast dye, hypertonic saline, mannitol, IVIG
→ Hypertonic dextrose (when administered without insulin)
● β2-adrenergic antagonists (non-cardioselective agents)
→ Interferes with the β2-mediated K+ cellular uptake/entry into
the cells
● Digoxin and related glycosides
→ Inhibits Na+/K+-ATPase, impairing/decreased K+ uptake by
muscles
→ Structurally related glycosides: yellow oleander, foxglove,
Bufo marinus (cane toad)
● Hyperkalemic periodic paralysis (HYPP)
→ Familial disorder
→ Episodes are precipitated by rest after exercise, either due to
K+ release from cells or inability to ingest K+ to enter cells
→ Hyperkalemia depolarizes muscle cells and unmask an
inactivation defect in skeletal Na+ channels (SCN4A mutation)
● Succinylcholine (muscle relaxant) 
→ Depolarizes muscle cells via AChR, causing efflux of K+
through the acetylcholine receptors
→ Contraindicated in thermal trauma, neuromuscular injury,
disuse atrophy, mucositis, prolonged immobilization
■ Will cause an exaggerated efflux of K+
■ Mechanism: marked increase and redistribution of AChRs
at the sarcolemma; depolarization causes exaggerated K+
efflux and acute hyperkalemia
● Severe tissue necrosis (rapid tumor lysis)
→ Extrusion of K+ from lysed cells
→ Acute tumor lysis syndrome, rhabdomyolysis
● Cationic amino acids
→ Lysine, arginine, ε-aminocaproic acid
→ Mechanism: cation-K+ exchanger of unknown identity and
mechanism
● Fluoride poisoning
→ Inhibits Na+/K+ ATPase activity
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021)
 | MUST KNOW
● Hyperkalemia occurs when:
→ There is decreased distal delivery of Na+, which will
stimulate K+ reabsorption (e.g., hypovolemia)
→ Drugs that inhibit ENaC (e.g., amiloride)
Inadequate K+ Excretion
● Inhibition of RAAS by drugs 
→ ACE inhibitors, Renin inhibitors (e.g. aliskiren), ARBs
→ Mineralocorticoid receptor blockers: spironolactone,
eplerenone, drospirenone (Yasmin-28)
→ Drugs that inhibit ENaC: amiloride, triamterene, trimethoprim,
pentamidine, nafamostat
→ Using in combination increases the risk of hyperkalemia
● Decreased distal delivery of Na+
→ Decreased distal Na+ delivery stimulates K+ reabsorption
→ Congestive heart failure, volume depletion/hypovolemia
● Hyporeninemic hypoaldosteronism
→ Tubulointerstitial diseases: SLE, sickle cell anemia,
obstructive uropathy
→ Diabetes, diabetic nephropathy
→ Drugs: cyclosporine, tacrolimus, NSAIDs, COX2 inhibitors, β-
blockers
→ Chronic kidney disease, advanced age
→ Pseudohypoaldosteronism type II
■ Hereditary hypertension with hyperkalemia
■ Mutations in WNK1 or WNK4 kinases, KLHL3, or CUL3
● Renal resistance to mineralocorticoid
→ Tubulointerstitial diseases: SLE, sickle cell anemia,
obstructive uropathy, amyloidosis, post-acute tubular necrosis
■ Hyperkalemia out of proportion to GFR
→ Congenital diseases
■ Pseudohypoaldosteronism type I
− Defect in the mineralocorticoid receptor or ENaC
channel
− Lifelong salt wasting, hypotension, and hyperkalemia
− Autosomal dominant: loss-of-function mutations in MLR
− Recessive: mutations in subunits of ENaC
■ Defects in the mineralocorticoid receptor and ENaC
● Advanced renal insufficiency 
→ Chronic kidney disease and ESRD
■ Very common causes of hyperkalemia due to the
associated deficit or absence of functioning nephrons
→ Acute oliguric kidney injury
■ Distal tubular flow rate and Na+ delivery are less limiting
factors in non-oliguric patients
→ Hyperkalemia out of proportion to the glomerular function rate
can also be seen in the context of tubulointerstitial diseases
that affects the distal nephron
● Primary adrenal insufficiency
→ Deficiency in mineralocorticoid and glucocorticoids producing
inadequate K+ excretion
→ Hereditary: congenital adrenal hypoplasia, congenital lipoid
adrenal hyperplasia, aldosterone synthase deficiency
Page 7 of 13
→ Autoimmune: Addison disease, polyglandular
endocrinopathy
→ Infectious: HIV, TB, CMV, disseminated fungal infection
→ Infiltrative: amyloidosis, malignancy, metastatic cancer
→ Drug-associated: unfractionated heparin, LMWH
→ Adrenal hemorrhage or infarction (e.g., APAS)
Excess Intake 
● Excessive intake is rare but may provoke hyperkalemia in
patients with predisposing conditions
→ Foods rich in potassium
■ Tomatoes, bananas, and citrus fruits
■ K+-containing salt substitutes (occult source)
→ Predisposing conditions U
■ Diabetics with hyporeninemic hypoaldosteronism
■ Chronic kidney disease (CKD)
● Iatrogenic causes
→ Overreplacement with KCl
→ Potassium-containing medications (e.g. K+-penicillin)
→ Red cell transfusion (especially massive transfusion)
B. CLINICAL FEATURES
Cardiac Complications
● Cardiac arrhythmias: sinus bradycardia, sinus arrest, slow
idioventricular rhythms, ventricular tachycardia, ventricular
fibrillation, and asystole 
● Progressive ECG changes
→ Actual findings 
■ 5.5-6.5 mEq/L: tall peaked T waves
■ 6.5-7.5 mEq/L: loss of P waves
■ 7.0-8.0 mEq/L: widened QRS complex
■ >8.0 mEq/L: sine wave pattern
− Impending ventricular fibrillation or asystole
→ Note that progressive ECG changes are insensitive, especially
in patients with CKD or ESRD
● Theoretical
→ Mild increases: affect repolarization; changes in T wave
→ Further increase: depressed conduction; prolongation of PR
and QRS intervals
→ Severe: loss of P wave; progressive QRS widening
→ Sine-wave sinoventricular rhythm
● Type I Brugada pattern on ECG
→ Pseudo-right bundle branch block and persistent coved ST
segment elevation in at least 2 precordial leads
→ Differentiated from genetic Brugada’s syndrome by: absence
of P waves, marked QRS widening, and abnormal QRS axis
Figure 10. Electrocardiographic changes in hyperkalemia.
Muscle Effects
● Secondary hyperkalemic paralysis
● May present with diaphragmatic paralysis and respiratory failure
● Expected findings on DTR: hyperreflexia 
Renal Complications
● Inability to excrete acid leading to metabolic acidosis 
→ Hyperkalemia has negative effects on acid load excretion
→ Due in part to competition between K+ and NH4+ for
reabsorption by the TALH
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021) Page 8 of 13

■ Subsequent countercurrent multiplication, ultimately ● If there are no causes of the transcellular shifts or increase K+
reduces the medullary gradient for NH3/NH4+ excretion by intake
the distal nephron → Check if there is decreased urinary K+ excretion (<40
● Restoration of normokalemia usually corrects the hyperkalemic mmol/day)
metabolic acidosis → Check the urinary electrolytes
■ If urine Na+ is <25 mmol/L, think of decreased distal Na+
C. DIAGNOSTIC APPROACH
delivery
● First priority is to establish if the patient needs emergency ■ Repletion of 0.9 NaCl or plain NSS or with furosemide
management due to hyperkalemia depending on the volume status, will reduce the plasma K+
→ This should be followed by comprehensive workup to concentration
determine the cause ■ If urine Na+ is >25 mmol/L, compute for TTKG
● History and Physical Examination ■ If more than 8, think of reduced tubular flow secondary to
→ Medications: ACE inhibitors, NSAIDs, TMP-SMX advanced kidney failure or reduced ECV
→ Diet and dietary supplements ■ If less than 5, it may be secondary to reduced K+ secretion
→ Risk factors: Kidney Failure (GFR >20 ml/min)
→ Reduction in urine output − Plasma aldosterone, renin, and response to TTKG after
→ Blood pressure fludrocortisone may be necessary to determine
→ Volume status specifically the cause of inappropriately low TTKG in
● Initial laboratory tests hyperkalemia
→ Serum electrolytes
→ BUN, Crea, Plasma osmolality D. TREATMENT
→ Urinalysis: Urine pH, osmolality, creatinine, electrolytes → Medical emergency and urgent treatment for: 
→ To assess the status of the K+ of the patient and to compute ■ ECG manifestations of hyperkalemia
for TTKG ■ K+ ≥6.5 mEq/L in the absence of ECG changes
→ Mg2+, Ca2+, CBC → Urgent management includes:
Specific Associations ■ Admission to the hospital
→ Urine Na+ <20 mM ■ Continuous cardiac monitoring
■ Distal Na+ delivery is a limiting factor in K+ excretion ■ Immediate treatment (three stages)
■ Volume repletion with NSS or treatment with furosemide may − Immediate antagonism of the cardiac effects
be effective in reducing K+ concentration − Rapid reduction in plasma K+ by redistribution
→ Transtubular K+ gradient (TTKG)  − K+ removal
■ < 3: hypokalemia
Immediate antagonism of cardiac effects of hyperkalemia
■ >7-8: hyperkalemia
[𝐾 +]𝑢𝑟𝑖𝑛𝑒 𝑋 [𝑂𝑠𝑚]𝑠𝑒𝑟𝑢𝑚 ● Mechanism of action
𝑻𝑻𝑲𝑮 = → IV calcium serves to protect the heart
[𝐾 +]𝑠𝑒𝑟𝑢𝑚 𝑋 [𝑂𝑠𝑚]𝑢𝑟𝑖𝑛𝑒
→ Calcium raises the AP threshold and reduces excitability,
Diagnostic Approach to Hyperkalemia without altering the resting membrane potential (RMP)
→ By restoring the difference between resting and threshold
potentials, calcium reverses the depolarization blockade due
to hyperkalemia
● Recommended dose: 10 mL of 10% calcium gluconate (or 3-4
mL of calcium chloride) infused intravenously over 2-3 minutes
with cardiac monitoring
→ Effect starts in 1-3 min and lasts for 30-60 min 
→ Repeat dose if there is no change in ECG findings or if they
recur after initial improvement
● Hypercalcemia potentiates the cardiac toxicity of digoxin
→ Calcium will NOT bring down the K+ level, it will only stabilize
the membrane 
→ Use with extreme caution in these patients
→ ADD 10 mL of 10% calcium gluconate to 100 mL of 5%
dextrose in water and infuse over 20-30 minutes
Rapid reduction in plasma K+ concetration by redistribution
into cells
● Insulin 
→ Shifts K+ intracellularly
→ Recommended dose: 10 units of IV regular insulin with 50 mL
of 50% dextrose (D50W, 25 g of glucose total)
■ Infusion of 10% dextrose at 50-75 mL/h with close
monitoring of plasma glucose (prevents hypoglycemia) 4
Figure 11. Algorithm for Diagnostic Approach to Hyperkalemia. → Onset: 10-20 min, peaks at 30-60 mins, and lasts for 4-6h
● In a patient who presents with elevated K+ level, check if the → Bolus D50W without insulin is never appropriate, given the risk
cause is pseudohyperkalemia of acutely worsening hyperkalemia due to the osmotic effect
→ If yes, no further treatment is needed and you just may need of hypertonic glucose
to repeat serum K+ levels → In patients with glucose levels of ≥200-250 mg/dL, insulin
● If the patient presents with ECG changes, such as peak T waves should be administered without glucose, with close monitoring
or worse, widened QRS complexes (give insulin alone)
→ Start with the emergency therapy right away ● β2-adrenergic agonists 
→ Once stable, take complete history and PE → 10-20 mg nebulized albuterol (in the PH: salbutamol) in 4 mL
→ Look for evidence of transcellular shift or increase K+ load of NSS, inhaled over 10 min
then treat accordingly ■ Onset: ~30 min, peaks at 90 min, and lasts for 2-6h
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021) Page 9 of 13

■ ~20% of patients with ESRD are resistant Past medical history: Diagnosed with Sjogren’s syndrome 2 years
■ Should not be used without insulin ago; uses artificial tears (eyedrops) PRN; denies any other
→ Side effects: hyperglycemia and tachycardia medications
■ Check pulse rate before giving albuterol or salbutamol
■ Use with caution in hyperkalemic patients with known Physical Examination
cardiac disease Vital signs: BP 120/80; HR 75/min, regular; RR 12/min; T 37oC
● Intravenous bicarbonate Dry erythematous buccal mucosa
→ No role in acute treatment of hyperkalemia  MMT: 2/5 on all four extremities
■ Although this slowly attenuates hyperkalemia with DTR: Hyporeflexive
sustained administration over several hours Sensory exam: Unremarkable
→ Infused in isotonic or hypotonic fluid (150 mEq in 1 L of D5W)
Laboratory Examination
→ In metabolic acidosis, delayed drop in K+ occurs after 4-6 h of
isotonic bicarbonate infusion CBC
Hemoglobin: 125 g/L (120-158 g/L)
Removal of Potassium Hematocrit: 40% (40-50%)
● Cation exchange resins WBC: 7,000 cells/mm3 (5,000-10,000 cells/mm3)
→ Sodium polystyrene sulfonate (SPS)  Neutrophils: 65%
■ Exchanges Na+ for K+ in GIT, increasing fecal K+ excretion Lymphocytes: 35%
■ Dosage: 15-30 g of powder, almost always in a premade
Chemistry Panel
suspension with 33% sorbitol
Na+: 140 (136-146 mmol/L)
− Full effect is slow and may take 24 hours, usually
K+: 2.7 (3.5-5.0 mmol/L) L
requiring repeated doses every 4-6 hours
Cl-: 119 (102-109 mmol/L) H
■ Complications: intestinal necrosis (colon or ileum)
HCO-: 12 (22-26 mmol/L) L
− Rare but fatal complication
Mg2+: 0.8 (0.62-0.95 mmol/L)
− More common in patients administered SPS with enema Creatinine: 1.1 mg/dL (0.5-0.9 mg/dL) H
and/or in those with reduced intestinal motility
TSH: 0.4 (0.34-4.25 mIU/L)
■ Contraindicated in constipated patients since K+ is
Plasma osmolality: 280 mOsm/kg (280-295)
secreted via the fecal route
→ Calcium-based resins ABG
■ More appropriate for patients with increased ECF volume pH 7.33
→ Novel intestinal potassium binders  HCO- 12 mEq/L
■ Patiromer: binds K+ in exchange for Ca2+ pCO2 27 mmHg
■ ZS-9: exchanges both Na+ and H+ for K+ and NH4+ Urinalysis
■ These agents appear to lack the intestinal toxicity of SPS pH: 6.1
● Intravenous saline  Specific gravity: 1.001 L
→ Beneficial in hypovolemic patients with oliguria and decreased Protein: +1 H
distal Na+ delivery Glucose: Negative
● Diuretics (loop and thiazide diuretics)  RBC: 5-7/hpf (non-dysmorphic) H
→ Reduce plasma K+ in volume-replete or hypervolemic patients WBC: 3-4/hpf
with sufficient renal function for a diuretic response Casts: None
→ May need to be combined with IV saline or isotonic Bacteria: 0
bicarbonate to achieve or maintain euvolemia, and then give Urinary Electrolytes
the diuretics Na+: 35 mmol/L
→ Dialysis (if all medical management fails) K+: 40 mmol/L
■ If K+ becomes intractable to all medical management, you Cl-: 18 mmol/L
need to dialyze the patient
■ Hemodialysis: most effective and reliable method to Urine Osmolality: 389 mOsm
reduce plasma K+ concentration  Urine Protein: 160 mg/g
■ Patients with AKI: temporary, urgent venous access
■ Patients with CKD or ESRD: preexisting venous access
→ Amount of K+ removed during hemodialysis depends on: 
■ Relative distribution of K+ between ICF and ECF
(potentially affected by prior therapy for hyperkalemia)
■ Type and surface area of the dialyzer used
■ Dialysate and blood flow rates
■ Dialysate flow rate
■ Dialysis duration
■ Plasma-to-dialysate K+ gradient
→ Peritoneal dialysis: considerably less effective due to slow
clearance (but it can be used)
CASE 1
A 45-year-old female was brought to the ER due to generalized Figure 12. Electrocardiographic findings of the patient (Case 1).
weakness. She denies any vomiting nor diarrhea. She claims to Sinus rhythm with prominent U waves on leads II, III, V4-V6.
have been admitted 3 months ago for weakness and discharged
with improvement after being given unrecalled medications.
Review of systems: Occasional left flank pain
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021) Page 10 of 13

Laboratory and ECG Interpretations Impaired

Problem in
● Arterial blood gas: Simple metabolic acidosis bicarbonate Problem in acid
Pathophysiology acid
● Urinalysis PCT secretion
secretion
→ Urine pH: Still acidic reabsorption
→ Specific gravity appears low (diluted) Non-anion gap Non-anion gap
acidosis, acidosis, low urine
■ However, the patient is clinically dry → this indicates urine Non-anion
glucosuria, ammonium, and
concentrating defect gap acidosis,
Other findings generalized hypocitraturia.
→ Protenuria of 1+ aminoaciduria, Hypercalciuria,
low urine
→ RBC: Patient has hematuria phosphaturia nephrolithiasis,
ammonium
→ WBC: Not significant since patient is female bone disease
● TTKG = (Urine K+ x Plasma Osm) / (Uosm x Plasma K+) Fanconi’s
→ (40 x 280) / (389 x 2.7) = 10.7 H Associated
syndrome
Nephrocalcinosis Renal
● ECG: Sinus rhythm, prominent U waves on leads II, III, V4-V6 features Hyperglobulinemia insufficiency

Metabolic Disorder Present ● Patient’s manifestations and laboratory findings are consistent
● Hypokalemia and non-anion gap metabolic acidosis with type 1 (classic distal) RTA
→ Serum potassium: 2.7 mmol/L L → Low plasma K+
→ ABG: pH 7.33, HCO3 12 mEq/L, pCO2 27mmHg → Urine pH >5.5 (px: 6.1)
→ Anion gap: 140 – (119 + 2) = 9 (NV 8-12) → Nephrolithiasis
● Classic distal RTA occurs frequently in Sjogren’s syndrome
What is the most likely cause of hypokalemia? → It is the result of an immunologic attack on the collecting
*Refer to Appendix for Diagnostic Approach to Hypokalemia tubule, therefore causing failure of the H+-ATPase to be
● Patient: inserted into the apical membrane of type A intercalated
→ Urine K+: 40 mmol/L (it’s >15 mmol/g) cells
→ TTKG: elevated at 10.7 (it’s >4) Patient Management
→ BP: Normal, therefore check ABG ● Replace K+ loss simultaneously via oral and intravenous routes
→ ABG shows metabolic acidosis, so consider proximal RTA since patient is symptomatic (paresis) and with ECG changes
and distal RTA (prominent U waves)
■ DKA, amphotericin B, and acetazolamide are ruled out → Oral potassium citrate (since patient has metabolic acidosis)
based on history → Peripheral IV access: 20-40 mmol of KCl per 1 L of IVF, OR
Ultrasound of the Kidneys → Central IV access: hook to cardiac monitor at the ICU and
● Ultrasound was requested due to hematuria and left flank pain infuse at rates of 10-20 mmol/h of KCl
● Posterior shadowing in the renal calyx ● Maintenance alkali replacement since patient has metabolic
acidosis
→ Sodium citrate solution (Shohl’s solution)
→ Sodium bicarbonate tablets
→ Additional benefit: expand volume and corrects the secondary
hyperaldosteronism
CASE 2
N.L, a 60-year-old female balikbayan from San Francisco, USA
consulted due to weakness of lower extremities.
She is a known diabetic for the past 20 years and a known case
of CKD for the past 5 years. Since she arrived 10 days ago, she
has been eating fruits with each meal and drinking fruit juices
instead of water.
3 days prior to consult, she also noticed a decreased urine output.
Physical Examination
VS: BP 110/70, CR 92/min, HR 18/min, T 37.1oC, Weight: 60 kg
Marked proximal weakness, dry buccal mucosa and dry
Figure 13. Ultrasound findings of the patient (Case 1). axillae. There was no edema noted.
Renal Tubular Acidosis (RTA) Laboratory Examination
● Conditions in which the cause of metabolic acidosis is due to Chemistry Panel
decreased renal tubular H+ secretion Na+: 135 (NV: 136-146 mEg/L)
● 3 major types: type 1 (distal), type 2 (proximal), type 4 K+: 6.0 (NV: 3.5-5.0 mEg/L) H
Table 1. Renal tubular acidosis (RTA)
Cl+: 100 (NV: 102-109 mEg/L)
Type 2 Type 1 Type 4 Creatinine: 3 (NV: 0.5-0.9 mg/dL) H
eGFR: 16 mL/min L
General Plasma osmolality: 295 mOsm/kg H2O (NV: 280-295)
Pathology Proximal Classic distal Distal
Dysfunction ABG
Plasma K Low Low High pH: 7.30
HCO3- 15 mEq/L
Urine pH with
acidosis
<5.5 >5.5 <5.5 or >5.5 pCO2: 30 mmHg
Urine net charge Positive Positive Positive Urinary Electrolytes
Na+: 30 mEq/L
Fanconi’s lesion Present Absent Absent K: 39 mEq/L L
Urine Osmolality: 230 mOsm/kg H2O
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021)
Figure 14. Electrocardiographic findings of the patient (Case 2).
Peak T waves on leads V2-V4.
Laboratory and ECG Interpretations
● Arterial blood gas: Simple metabolic acidosis
● ECG: Peak T waves on leads V2-V4
Metabolic Disorders Present
● Hyperkalemia with high anion gap metabolic acidosis
→ Serum Na: 135 mEq/L
→ Serum Cl: 100 mEq/L
→ Serum K: 6.0 mEq/L H
→ ABG: pH 7.30, HCO3 15 mEq/L, pCO2 30 mmHg
→ Anion gap: 135 – (100 + 15) = 20 H
What are the most likely factors responsible for the elevation
of the plasma K+ (hyperkalemia)?
● Low urine K+ (39 mEq/L) is contributing to the hyperkalemia
→ With the patient’s increased potassium intake, the normal
renal compensation should be increased renal potassium
secretion
→ However, there is inappropriate renal response, probably due
to CKD (Stage 4)
■ The excess potassium cannot be excreted appropriately
● Metabolic acidosis
→ Aggravates hyperkalemia due to intracellular buffering of H+
with increased cellular K+ release from the cells to maintain
electroneutrality
Patient Management
● Administer calcium gluconate, 10 mL of 10% solution
infused over 2-3 minutes
→ Effect begins within minutes but is short-lived (30-60 min)
→ Dose can be repeated if no change in ECG after 5-10 min
→ This is given to stabilize the membrane
● Administer 10-20 units of regular insulin (HR) + 25-50 g of
glucose (D50W)
→ K+ will fall by 0.5 – 1.5 mmol/L in 15-30 min
→ Effect begins at 10-20 mins, peaks at 30-60 mins, lasts 4-6
hours
● Administer B2-adrenergic agonist (salbutamol
nebulization)
→ Onset of action: 30 minutes
→ Lowers plasma K+ concentration by 0.5-1.5 mmol/L, with the
effect lasting for 2-6 hours
● Loop Diuretics (i.e. furosemide)
→ Insulin and B2-adrenergic agonist will only have a temporary
result, and thus loop diuretics (such as furosemide) can be
administered as long as the patient is euvolemic to promote
renal K+ excretion
● Sodium or calcium polystyrene sulfonate
→ Cation exchange resins that promote exchange of Na+ for K+
in the GI tract
→ Dose: 15-30 g of powder in premade suspension with 33%
sorbitol
→ Full effect may take up to 24 hours and usually requires
repeated doses every 4- 6 hours
→ Contraindicated in patients with impaired bowel movement
● Hemodialysis
→ If everything was done, where all medical management was
given adequately to the patient, but the patient is still
hyperkalemic, this is the time you initiate dialysis
Page 11 of 13
■ This is called intractable hyperkalemia
■ Dialysis is an indication for intractable hyperkalemia
● Treat the underlying cause of hyperkalemia
→ Dietary modification
■ Patient has poor dietary control of potassium intake,
therefore modify the diet
■ Correction of metabolic acidosis
Treatment
● Removal of potassium
→ When giving K correction, make sure the IV is properly
inserted because it can cause burn
→ When oral K is given, always ask for history of ulcer (may
cause worsening GI distress)
→ Cation exchange resins
■ Sodium polystyrene sulfonate (SPS) exchanges Na+ for K+
in the GIT and increases the fecal excretion of K+
− Recommended dose of SPS H anis 15-30g of power
given in the premade suspension with 33% sorbitol
− Full effect may take up to 24H and usually requires
repeated doses evert 4-6H
− S/E: Intestinal necrosis of the colon or ileum – rare but
fatal complication
− Do not give to patient with a history of GI bleeding or
constipation, may also cause esopagitis
■ Calcium-based resins more appropriate in patients with an
increased ECFV
→ Diuretics
■ Used in volume-replete or hypervolemic patients with
sufficient renal function
■ May need to be combined with IV saline or isotonic
bicarbonate to achieve or maintain euvolemia
→ Dialysis
■ Hemodialysis is the most effective and reliable method to
reduce plasma K+ concentration
■ Peritoneal dialysis is considerably less effective
Q&A
If there’s an absolute indication for dialysis like uremia and
there exists for relative indications like hyperkalemia that’s not
intractable, does dialysis address this?
● Of course, if there’s other indications for dialysis like if you
remove uremia, hyperkalemia will also be removed
● You don’t have to have all the indications like intractable volume
overload, intractable metabolic acidosis, you don’t have to wait
for intractable hyperkalemia, if you have one indication for
dialysis, by all means do the dialysis immediately
If we give diuretic to our patient, is it still okay if we give cation
exchange resin?
● Still okay but think about the level of the K+ and ECG changes of
the patient first
● Since diuretic will go down quickly whereas for the cation
exchange resin you will have to wait for one or two days for it to
go down
● You can still give but if you want to immediately see the effect of
the decrease in potassium level, the diuretics would be more
appropriate
● Let’s just say the K+ decreased to 5.7 from 6.5 after administering
diuretic, maybe that’s when you can give your cation exchange
resin cause you don’t need to urgently decrease the K+ level of
the patient
For patient who has diarrhea and vomiting with hypokalemia, is oral
KCl still the treatment for the patient or should it be IV KCl infusion?
● If you compare the need for increased absorption of K+, the
fastest would be through the oral route. Though the downside of
the oral route is if the patient is vomiting, they cannot take it orally
and it’s painful for the stomach
● So if the patient is still experiencing diarrhea and vomiting, the
best management would still be an IV KCl correction
 ME2D-NEPH 1.18 –Potassium Disorders (09 SEPTEMBER 2021; 23 NOVEMBER 2021) Page 12 of 13

● Two benefits: IV can be corrected and the you can still correct
volume loss through IV
● But once the patient is not vomiting that much anymore, oral
route is preferred since absorption is faster as long as there is no
vomiting, abdominal pain, history of ulcers or GI bleeding. Those
are the things we look for if we want to shift to oral route.

Is there a way to lessen the pain when giving K+ to patients via

IV?
● Make sure IV is properly inserted (if not properly inserted, may
cause burns) and dilute the KCl (IV correction will be given
multiple times)
● Let’s just say we correct it for 4 hours, prolong the correction to 6
hours so that the KCl will not be administered too fast

What should be done if during insulin administration of

hyperkalemia patient, the patient becomes hypoglycemic?
● Give D50
→ D50mL (50% Dextrose)
→ Must know CBG of patient
→ When the patient shows up at the ER, give them the works:
cardiac monitor, check CBG
→ If CBG is normal, give D50-50 + insulin
→ If CBG is around 250, give Insulin right away (sugar will not
decrease right away and become less than <70mmL)
→ If a patient’s diabetic status is unknown, it is best to frequently
monitor CBG
END OF TRANSCRIPT
REFERENCES
Laguesma-Navarro, R.J., (2021), Workshop on Potassium Disorders [PowerPoint
Presentation]. Manila, Philippines: Faculty of Medicine and Surgery, University of
Santo Tomas, MED 2

Jameson J.L, Kasper, D.L., Longo, D.L., Fauci, A.S., Hauser, S.L., Loscalzo, J.
(2018). Harrison’s Principles of Internal Medicine. USA: McGraw-Hill Education.
(Chapter 49, pp. 304-312)

Original Transcribers:
B2023 TWG 16 | CUENCA, DE GUZMAN, FIGUEROA, FRANCISCO, HENSON,
LACSON
TEG 9 | CRUZ, DE BELEN, GAMBOA, GONZAGA, HUELAR, LAGMAY
TC: LICLICAN, C
B2022Tarrosa, Tandoc, Tanag, Tatad, Tecson, Tendenilla, Terencio
 MEDICINE 2 – [NEPHRO]: GENERAL LECTURE AY 21-22

09 SEPT 21
Dr. Romina Jasmin Laguesma-Navarro 23 NOV 21

Diagnostic Approach to Hypokalemia

A-TG14 | CABILLAR | CACHUELA, CALIMAG, CAMPOS, CANIVEL, CANLAS Page 13 of 13