Lecture 17: Disorders of Potassium Balance, Hyperkalemia Flashcards
What are the key characteristics of hyperkalemia?
Hyperkalemia > 5 mEq/L Can be acute or chronic Can present in three ways i. normal total body K content ii. high K body content iii. low K body content Can be iatrogenic and fatal
What are the key factors that regulate K internal balance?
- Insulin
- Catecholamines
- Aldosterone
- Posm
- Acid-base status
- Na/K ATPase
Why is hyperkalemia a problem?
Gain of ICF K = cell swelling = cell alkalosis (since K and H always interchange)
More ICF K = more inactivation gates closed for Na (since membrane potential is depolarized)
Can lead to muscle excitability
Hyperkalemia also leads to conduction issues in the heart
Hyperkalemia can also lead to vasodilation of SMCs
What are the clinical manifestations of hyperkalemia?
- ECG changes and cardiac arrhythmias
- Muscle weakness, paralysis
-cells depolarize
-increased membrane excitability initially
But Then
-persistent depolarization reduces membrane excitability due to Na channel inactivation - Paresthesia
- Impaired urinary acidification
What are the ECG manifestatiosn of hyperkalemia?
Peaked T waves (V2-V4)
Prolonged PR interval
Flattening or absence of p waves (the greater the hyperkalemia)
Wider QRS complex
Severe hyperkalemia ECG abnormalities evolve within seconds
Correlation between K levels and ECG is imprecise
What are the causes of hyperkalemia?
- Too much K intake
- Too little K excretion
- lysis of cells which release K into the ECF
Usually patients have defect in at least 2 of these factors
What is pseudohyperkalemia?
When potassium levels are elevated due to release of K from cells either during or after blood specimen is obtained in ABSENCE of true elevated serum K concentration
Serum concentration collected after the blood clots
However, if serum is put on the slide too rapidly or is roughly handled, can cause RBC and WBC after blood is drawn from person
-this leads to elevated SERUM K concentration, but there is a normal PLASMA K concentration
What are causes of pseudohyperkalemia?
- In vitro hemolysis
- Leukocytosis (WBC>70,000/cm^3)
- plasma K normal but serum K is high
- Thrombocytosis (platelet count > 500,000cm^3)
- plasma K normal but serum K is high
- Fist-clenching during blood drawing (isn’t this what I do all the time?) if arm is wrapped in a tourniquet…breakdown of muscle?
What are the characteristics of hyperkalemia due to excessive intake?
Excessive K intake alone is almost never the cause alone
Can only cause more than mild transient hyperkalemia if there is impairment of K excretion in the other two causes
If you do want to cause hyperkalemia, then you have to have chronic K intake
That is because distal tubule can secrete crapload of K from collecting tubule
What are the most common dietary sources of hyperkalemia?
- potatoes, avocados, cantaloupe, bananas, oranges, fruit juices, tomatoes
- salt substitute
- health food/nutritional supplements
- parenteral nutrition/enteral feedings (iatrogenic)
What is recommended daily potassium intake?
4,500 mg per day
What are the most common medications that can cause hyperkalemia?
- K supplement (KCl)
- Polycitra-K: 2 mEq/ml
- Neutra-Phos/Neutra-phos-K: 7-14 mEq/dose
- Potassium penicillin: up to 41 mEq/daily dose
What are the characteristics of hyperkalemia due to too little excretion?
- Low GFR
- acute kidney injury (AKI)
- chronic renal disease (CKD)
- Impaired RAA axis
- Inadequate distal Na delivery and urine
- reduced aldosterone synthesis
- reduced responsiveness to aldosterone
What are conditions that lead to low GFR (and thus hyperkalemia?
- acute kidney injury (AKI)
2. Chronic renal disease (CKD)
What is the difference between acute and chronic kidney disease with relation to hyperkalemia?
Acute = compensatory mechanisms don’t have time to kick in yet Chronic = already compensation in terms of tubular hyperplasia of principal cell BLM area, increase Na/K atpase activity and increased apical K channel activity
What are the conditions that lead to RAAS impairment?
- Reduced aldosterone synthesis
2. Reduced responsiveness to aldosterone
What are the potential causes of reduced aldosterone synthesis?
- Addison’s disease (adrenal insufficiency)
- Genetic disorders
-Congenital adrenal hyperplasia
-Aldosterone synthase mutations - Type IV RTA with hypreninemic hypoaldosteronism
- Drugs like NSAIDs, ACEi and ARBs, cyclosporine, tacrolimus, heparin
MoA slide 12 of lecture - HIV, Tb, fungal infections, infarction can also mess with adrenals
What does RTA stand for?
Renal Tubular Acidosis
Involves accumulation of acid due to failure of kidneys to appropriately acidify the urine
What is pseudohypoaldosteronism (PHA)?
When distal nephron is poorly responsive to aldosterone due to genetic reasons
Thus, lack of aldosterone response is NOT due to lack of aldosterone in the body
PHA1 = due to defect in ENaC or Mineralocorticoid receptor
PHA2 = gordon’s syndrome = dysfunction of kinase system that regulates Na-Cl symporter in DCT
What are the causes of impaired aldosterone responsiveness?
- Drugs
- Tubulointerstitial kidney disease (will be covered later)
Ie drug induced interstitial nephritis, kidney transplant rejection, etc - Pseudohypoaldosteronism
- Anything that scars the collecting duct
What drugs impair aldosterone responsiveness?
- Amiloride (direct ENaC inhibitor)
- Spironolactone and Eplerenone (MR antagonists)
- Triamterene, trimethoprim, pentamidine (ENaC inhibitors too)
Thus these drugs are common causes of hyperkalemia
What is Trimethoprim used for?
Antibiotic used with Sulfamethoxazole to treat Pneumocystis jirovecii
Can cause HYPERkalemia
What are acute causes of abnormal internal balance leading to hyperkalemia?
- insulin deficiency
- hypertonicity
- metabolic acidosis
- drugs
- exercise
- muscle necrosis and cell lysis
- Hyperkalemic periodic paralysis
- intermittent episodes of acute translocation of K from ICF to ECF
How can digoxin lead to hyperkalemia?
By blocking Na/K pump, so potassium stays in plasma
What are causes of rhabdomyolysis?
When alscoholics or drug users sleep on hard surfaces, causing ischemic pressure injury to muscle
Also can be caused by cocaine and ecstasy, malignant hyperthermia, hypophosphatemia, and extreme exertion, trauma
What are the characteristics of hyperkalemic periodic paralysis?
Intermittent episodes of acute translocation of K from ICF to ECF
Rare disorder
What happens to plasma K when one fasts?
Plasma K increases because there is no insulin to secrete K (or activate Na/K) as one is fasting
What happens to plasma K when one adds effective osmoles?
Effective osmoles = mannitol, glucose, NaCl, NaHCO3
Adding effective osmoles that stay on the ECF side of things will draw K from ICF to ECF
Due to:
i. solvent drag
ii. paracellular diffusion due to inherent increased K concentration (because water is being lost, thereby further concentrating K+)
What is the relationship between blood glucose levels and hyperkalemia?
The more glucose in blood = greater plasma K concentration
Seen in DKA and hyperosmolar, hyperglycemic non-ketotic (HHNK) syndrome
What is the effect of metabolic acidosis on hyperkalemia?
Acute metabolic acidosis can cause TRANSIENT hyperkalemia
Mechanism: increased ECF H+ will enter the cell and K+ will diffuse out to compensate
What is the difference between HCl and beta hydroxybutyric acid (B-OH-B) on K secretion to ECF?
HCl infusion into portal vein does NOT induce insulin secretion so there is high level of K acutely
B-OH-B on the other hand does upregulate insulin secretion so there will be an increase in K secretion, thus a decrease in plasma K concentration
How does one evaluate patient with hyperkalemia?
With TransTubular Potassium (K) Gradient (TTKG)
TTKG = [urineK/plasmaK]/(Uosm/Posm)
TTKG used to assess K secretion by collecting duct and urinary K excretion
What is the greatest utility of TTKG?
Can tell the difference between hypoaldosteronism or aldosterone resistance
TTKG > 6 after MR administration suggests hypoaldosteronism with normal responsiveness
TTKG < 6 after MR administration suggests either hypoaldosteronism and/or aldosterone resistance
TTKG normally = 7-10 and is usually >10 as K secretion increases
What is the emergency treatment for severe acute hyperkalemia?
- Antagonize cardiac (ECG) effects
- Move K from the ECF into cells
- Remove K from the body
How does on antagonize the cardiac effects?
- calcium gluconate
-MoA not clear, but it increases threshold potential at which excitation occurs
-increases number of membrane Na channels resulting in faster conduction
Thus you need to use calcium to counteract ECG effects of hyperkalemia
-calcium infusion does NOTHING to serum K
Calcium infusion makes the threshold for action potential higher, so greater separation between resting membrane potential of K and what is necessary depolarization
How does one move K into the cells as part of hyperkalemia treatment?
- Insulin
- B2 agonists
- sodium bicarbonate
How does insulin help move K into cells?
Stimulates muscle and liver cell uptake of K
MoA: insulin stimulation of Na/K ATPase
How does B2 agonists move K into cells?
Increase cellular uptake of K by stimulation of Na/K ATPase in muscle and liver
Example: nebulized albuterol (for asthma)
MoA: stimulation of Na/K ATPase
How does sodium bicarb move K into cells?
As more bicarb is in the ECF, more H+ will exit the cell to combine with HCO3-
Thus, the H+ efflux will upregulate K+ influx
Only effective in severe metabolic acidosis
Thus is NOT normally used
How does one remove K from system?
- Loop diuretics
- Cation exchange resin-sodum polystyrene sulfonate
Kayexalate - Hemodialysis
How do loop diuretics remove K from system?
Blocks NKCC2 so less K uptake in TAL
Only increases urinary K excretion if and only if ECF volume and urine output is maintained
Response to loop diuretics is variable
Thus do not use loop diuretic for acute cases
Only use loop diuretic for CHRONIC management of chronic hyperkalemia
How does loop cation exchange resin remove K from system?
Aka Kayexalate
Resin binds K (and Ca and Mg) in exchange for Na
Administered orally with sorbitol (to forestall constipation) or as retention edema
Onset of action: 1-2 hours
How does hemodialysis remove K from system?
Can remove 60-120 mEq K during a 4 hour treatment
So it is most effective for patients with severe hyperkalemia
Used when patient has significant renal failure, so increasing urinary K excretion is not an option
How does one manage chronic hyperkalemia?
- Diuretics
- Kayexalate
- Reduce intake
- Review medications
- Increase Na intake (NaCl and NaHCO3)
- Fludrocortisone
