R4 Hypokalemia and hyperkalemia

Hypokalemia - serum potassium concentration less than the normal range of 3.5-5.5mEq/L

Hyperkalemia - serum potassium concentration greater than the normal range of 3.5-5.5mEq/L

• ICF (98%) >>>>>> ECF
• Intra-cellular vs extra-cellular balance; intracellular balance is critical for minimizing transient changes in serum K+
• Urine is major excretory pathway; stool in some  states

1. β2 agonists - catecholamines for tx of asthma, hypertension, angina

• 2. insulin - diabetes mellitus
• - often used in the treatment of high K+ (shifts K+ into cells)

3. Body fluid tonicity - diabetes mellitus

4. hypertonicity effects water and K+ movement out of cells (solvent drag)

• 5. acid-base balance -- intracellular buffering (K-H exchange)
• -Mineral acidosis, metabolic alkalosis

• Intake: rarely the problem
• -High intake rarely causes high serum K, unless there are reasons for compromised excretion or internal balance
• -low intake rarely causes low serum K, unless it is coupled to augmented excretion

• Excretion:
• -Kidney>>>>>GI tract (90%/10%)
• -Urine K+ varies with intake; kidney can increase K+ excretion rapidly in response to increase in serum K
• -Kidney conservation of K is less rapid (days to weeks to maximize)

• filtered at glomerulus
• reabsorbed by proximal tubule and TAL
• excretion (and serum concentration**) controlled by distal tubular secretion (DCT)
• -excretion is highly regulated

• Regulation of distal tubular K+ secretion: increases/decreases
• 1. Serum K+
• 2. Aldosterone/responsiveness to aldosterone
• 3. Distal tubular flow rate 
• -increased flow leads to kaliuresis (volume expansion, 1^o hyperaldosteronism, diuretics acting proximal to DCT, osmotic diuretics, metabolic alkalosis)
• -decreased flow can lead to K+ retention (volume depletion, low effective arterial volume; K-losing tendencies of primary hyperaldosteronism is blunted by low sodium intake)

• 4. Acid-base balance
• -alkalemia increases (and acidemia decreases) uptake of potassium from peritubular capillary into the tubular epithelial cell
• -Acute metabolic/respiratory alkalosis enhances K+ secretion and excretion
• -Acute metabolic/respiratory acidosis blunts potassium secretion/excretion
• -Chronic metabolic alkalosis shows marked kaliuresis, low serum potassium, very low total body potassium

• -Acidosis: decreased potassium secretion/excretion
• -Alkalosis: increased potassium secretion/excretion

5. Drugs (K-sparing diuretics)

6. Anion delivery

7. Sodium delivery

• -History, physical
• -medication use
• -lab vallues
• -TTKG

*Most patients with hyperkalemia have multiple defects in potassium homeostasis

• Transtubular K+ Gradient:
• -used to assess whether the kidneys are responding appropriately to the low or high K+
• -reflects the driving force for K+ secretion in CD
• -TTKG = [UK⁺/blood K⁺] x Posm/Uosm

• Nl kidney: problem is extra-renal
• -Hyperkalemia: TTKG >6
• -Hypokalemia: TTKG <3

• Abnormal kidney: problem with the kidney
• -hyperkalemia: TTKG <6
• -hypokalemia: TTKG >3

Hyperkalemia is due to extra-renal problem

• 1. Increased intake
• -Fruits, Vegetables

• 2. Cellular shift
• -Pseudohyperkalemia
• -Acidosis
• -Insulin deficiency
• -β-blockers
• -Digoxin
• -Tissue necrosis
• -Periodic paralysis

Hyperkalemia related to impaired renal function

• 1. Hypoaldosteronism
• -Spironalactone
• -NSAIDs
• -ACE-In
• -ARB
• -Renin inhibitor
• -Type 1 and 2 PHA
• -Adrenal insufficiency
• -Hyporeninemia

• 2. Reduced Na+ uptake
• -Decreased ECV
• -Triamterene
• -Amiloride

• 3. Low GFR
• -Acute and chronic kidney disease

• Abnormal cardiac muscle depolarization and repolarization
• -Peaked T waves
• -Shortened QT interval
• -Widening of QRS
• -disappearance of the P wave
• -"sine wave pattern"
• -Ventricular fibrillation
• -_{skeletal muscle weakness} (completely unimportant finding)

• Rule out pseudohyperkalemia
• -lab error due to lysis of cells in tube; leukocytosis and thrombocytosis
• -repeat with fresh blood draw

*Tx not evidence based in terms of what Rx to give at what K+ level

• Tx that promotes K+ shift into cells
• 1. Calcium chloride
• -K+ raises the resting membrane potential; Ca2+ raises the threshold potential so that the difference is what it normally is (or near normal)
• -temporary effect: lasts ~1hr

• 2. IV insulin and glucose
• -drives K+ into the cells
• -lasts for hrs

• 3. Nebulized salbutamol (β agonist)
• -lasts for hrs

• Tx that promotes K+ loss
• 1. Cation exchange resin (Kayexelate)
• -causes diarrhea

2. Loop diuretics (if normal ECV)

3. Dialysis (if ESRD)

• Inadequate intake (rare)
• Cellular uptake
• Nonrenal loss
• Renal loss (high blood pressure vs normal/low BP)

Extrarenal cause for hypokalemia - kidney is trying to hold on to K+

• 1. Decreased intake
• -Geophagia ('eating dirt')

• 2. Cellular shift
• -Alkalosis
• -Insuline/Glucose
• -β2-agonists
• -Cell proliferation
• -Periodic paralysis

• 3. GI loss
• -Diarrhea
• -Laxative abuse

Hypokalemia due to renal problem; inappropriately elevated TTKG

• Evaluation:
• 1. BP
• 2. pH (if blood pressure is normal or low)
•      A. RT_A (if pH is low)
•      B. Vomiting, Diuretics, Bartter's syndrome, Gitelman's syndrome (if pH is high)
• 3. Renin (fi blood pressure is high)
•      A. Renal arterial stenosis (if Renin is high)
• 4. Aldosterone (if renin is low)
•      A. Primary hyperaldosteronism, GR_A (if Aldosterone is high)
•      B. Cushing's syndrome, congenital adrenal hyperplasia, _AME, LIddle's syndrome (if Aldosterone is low)

• -Estimate K+ deficit; but complicated due to alterations in internal balance
• -If uncomplicated, plasma K decreases by approximately 0.3mEq/L for each decriment of 100mEq total body K

• -Asymptomatic: hypokalemia is treated with oral KCl replacement
• -IV KCl can be used in pts with symptoms

• -Rate of replacement: must consider severity of the hypokalemia, pt's underlying disease
• -Avoid rates >10-20mEq/hr (risk of overcorrecting to hyperkalemia)