W2 Hypo/Hyperkalemia (Joey) Flashcards
Hypokalemia
What are the 6 main reasons?
Reasons:
—emesis — GI loss, HCL loss
—RAAS system activation — NA+/K+ pump secreting K+ into urine
—diarrhea
—increased insulin, leads to increase in K+ uptake
—hyperaldosteronism
—loop diuretic use
Definitions:
● Hypokalemia = Low Potassium Levels in the Blood (serum)
● Laboratory definition of Hypokalemia being a
serum K+ of < 3.5 meq/L.
PO Intake is the 1* source of K+, and PO K intake is usually way above physiological needs
Plasma K+ poor indicator of body content: it’ll keep coming back unless you remove what’s already there
Potassium intra/Extracellularly
Laboratory definition of Hypokalemia is a serum K+ of < 3.5 meq/L.
● Note that serum potassium level is different than the concept of Total Body Potassium (which takes into account both INTRAcellular K+ & EXTRAcellular K+)
○ Intracellular K+ = K+ within the somatic cells themselves, easy right?
■ Intracellular K+ makes up about 98% of total body K+
○ Extracellular K+ = the K+ within the serum, the lymphatic vessels, and the interstitial fluids/spaces (however clinically extracellular K+ can be thought of for all intents and
purposes as being the same as Serum K+)
■ Extracellular K+ makes up about 2% of the total body K+
○ Intra & Extracellular K+ balances are primarily maintained physiologically by the kidneys (via intentional renal K+ reabsorp/sec), & the cell surface Na+/K+ pumps (for
most somatic cells, this often involves exchanging 3 Na+ in for 2 K+ out - though
these #s are not always the case - remember our best friend the collecting duct of the nephron)
■ This Na+ & K+ balance mech. is how the cells maintain resting membrane potential
Signs and symptoms of HYPOkalemia
EKG
GI (2)
Muscles
Signs of Hypokalemia:
● Often related to systemic (striated & non-striated) muscle contraction dysfunction (as low serum K+ in relation to high intracellular K+ leads to a state of abnormal resting cell membrane potential, specifically the >K+ levels in the cells, compared to the <K+ extracellularly, leads to a net hyperpolarization state within the cells, making the cells less likely to depolarize in the setting of stimulus, leading to
< muscle contraction), some examples of this phenomenon include:
○ Skeletal muscle weakness, constipation, respiratory depression (diaphragm), cardiac contractility dysfunction
○ EKG: Hypokalemia may show on EKG as prolonged QT interval, U wave, +/- tachyarrhythmias (but often with poorer cardiac output)
Symptoms of Hypokalemia:
● Generalized and muscle fatigue, malaise, muscle cramping, constipation, SOB, palpitations (many other examples as well)
—Decreased potassium available from GI absorption (diarrhea)
—Decreased PO intake, chemo patients, chronic emesis, anorexia
—Increase in intracellular shift of K+ into the cells
insulin promotes intracellular intake of K+, glucose and phosphorus
—Increased renal K+ secretion
AKI, hyperaldosteronism
Hypokalemia:
Causes & Patho: Increase in Renal K+ Secretion
Emesis
RAAS system activation
● Emesis:
○ Emesis leads to GI loss of HCL ( think: H+ / Cl- ). Notably the loss of H+ ions from an acid/base buffer system standpoint leads to a (transient) increase in free serum bicarb (HCO3-). This increase in serum bicarb at the level of the nephron leads to decreased reabsorption of bicarb
from the filtrate in the nephron lumen. This leaves more bicarb in the nephron lumen as part of the filtrate, creating a net increase in the electronegativity of the filtrate solution itself. This increased net electronegativity of the filtrate, from a charge standpoint, leads to more K+ being held onto in the filtrate solution to help “neutralize” that increased net electronegativity.
RAAS System Activation (many causes, see chart in last slide for how we got there…):
○ Increased RAAS system activity downstream leads to (2 points here):
■ 1. Transient increased levels of serum AT2 (& Aldosterone), leading to increased collecting duct expression of the ENaC transporter (whose role is to promote Na+ reabsorption). While Na+ is shifted back into the serum, Cl- is left behind in the filtrate (then see intraluminal electronegativity effects on K+ pull discussion above).
■ * 2. Transient increased levels of serum aldosterone (released from adrenal cortex). The increased levels of serum aldosterone leads to increased surface expression and activity of the Na+/K+ ATP-ase pump in the collecting duct, which promotes Na+ reabsorption and K+ secretion into nephron tubule → loss of K+ into the urine
Hypokalemia:
Causes & Patho - Decreased K+ Availability for GI Absorption
Actual Decreased Intraluminal GI K+ Levels:
○ Diarrhea !!!!
○ Secondary to decreased PO intake, so meaning that the serum K+ levels are too low because the body not taking in enough K+ to even be absorbed (this is super uncommon if the body is taking in regular PO given how abundant K+ is in food, however which syndromes can you think of where PO-associated intake of K+ may be decreased?)
Normal (or High ← rare) Intraluminal GI K+ Levels, but the K+ is Unable to be Absorbed Well:
○ Excessive GI Potassium Binders / Chelators:
■ Exs: Kayexalate, Patiromer (tx for hyperkalemia)
■ It is uncommon for these medications to cause hypokalemia because they’re not super strong or fast acting on their own (unlike insulin which is more rapid onset), AND you don’t give them to patients who don’t have hyperkalemia (makes sense right?)
○ A Long Term SE of Bowel Resections (in the GI tract most K+ is absorbed by the distal small bowel and large intestine):
■ Exs: Urinary diversions via small bowel (cystectomy w/ ileal conduit), Short Bowel Syndrome from multiple prior bowel resections (surgeries for IBD, GI cancers, etc)
Hypokalemia:
Causes & Patho - Increased K+ Shift Into Cells
Increased Serum Insulin / Increased Insulin Activity:
○ Insulin Spikes & Exogenous Insulin: Speaking easily, insulin MOA promotes muscle and fat cell uptake of glucose, K+, and phos, therefore leading to fast & significant < in serum K levels
○ Refeeding Syndrome: Also primarily insulin mediated, but multifactorial, speaking easily… after a somatic cell is chronically deprived of glucose / nutrients from < nutrient intake (ex: usually < PO), but then the body subsequently is able to take in nutrition (pt starts taking in PO), this leads
to increased available serum glucose / nutrients to the cell, the cell then finally takes in as much nutrients as it can (think glucose and K+ as above), therefore leading to < serum K+
Increased Red Blood Cell Production:
○ Complicated physiology, however increased red blood cell production (think: really hyperproliferative cellular production / high intracellular metabolic processes) leads to increased cellular uptake of K+, therefore decreasing serum K+ levels
Beta 2 Receptor Stimulation:
○ Endogenously or exogenously (meds)…. regardless beta 2 receptor stimulation leads to increased activity of the Na+/K+ ATP-ase pump on muscle cells, resulting in K+ influx (K+ going into the muscle cells) and Na+ efflux, therefore decreasing serum K+ levels
Hypokalemia:
Other Specific Notable Causative Factors
Hyperaldosteronism:
○ A state of excessive serum aldosterone (2/2 genetic factors, CHF, etc)
■ Primary Hyperaldosteronism: Excessive production of aldosterone in the adrenal gland itself (may be malignant or non-malignant in etiology)
■ Secondary Hyperaldosteronism: Excessive RAAS activation leading to excessive release of aldosterone (via ex: renin-producing tumors, renal artery stenosis leading to increased renin secretion)
○ More to come on this in endocrinology, however the > aldosterone leads to > Na+ reabsorption and > K+ secretion → <serum K+ levels
Loop Diuretic Use:
○ LDs promote K+ secretion (via a few mechanisms) in the nephron (as well as Na+), which may lead to < serum K+ levels
■ * LD use is quite commonly a/w <K+, & often pts on chronic LDs need to also be on concurrent K+ PO
repletion while they are taking LDs to offset the assoc. K+ loss (common to see lasix + KCl on med list)
■ Loop diuretics are often used 1st line in the hospital setting to treat acutely hypervolemic pts (ex acute
volume overload 2/2 acute HF exacerbation). If diuretic therapy is needed in a pt who has severe hypokalemia and you cannot stop diuresis, you can also consider changing to a K+ sparing diuretic instead
Hypokalemia:
Possible EKG Findings
● * QT Prolongation
● Mild: Presence of a U wave (sometimes misinterpreted as prolonged QT when the T wave and U wave merge)
● More severe: T wave inversion, prominent U wave
● Most severe: severe repolarization difficulties, eventually may lead to Torsades
Hypokalemia
Treatments
● Step 1: Try to identify the cause!
○ Step 1 sub a: Fix it :)
■ Exs: If pt having emesis or diarrhea, then treat the nausea cause of v/d, if pt on a potassium wasting diuretic, switch it to a potassium sparing diuretic, if pt simply having < PO K+ intake then give PO K+ *, etc
■ There are times when the causative factor of hypokalemia is acute treatment of another disease state (ex. giving a pt exogenous insulin for a severe hyperglycemia)
● After weighing the +/-s on both sides, you may determine that you cannot (or should not) stop the cause… in cases like these, you may just need to exogenously replete the K+
● Step 2: Replete the K+
○ K+ repletion (via PO & IV KCl) is a common and consistent component of hypokalemia treatment regardless of cause, because either way, they need more serum K+
○ Typically given PO 1st line (given <$, however pills are huge and can cause GI discomfort)
○ If pt NPO (think: emesis, AMS, etc), then you can replete IV (but pt must be on tele for IV)
○ It’s equivalent dosing for PO and IV K+, however IV K+ tends to increase serum K levels much faster (>K usually shows up on BMP 1+ hours after IV K+ given, PO make take >4 hrs)
Hypokalemia
Treatments continues
● What to do when K supplem and tx of the apparent causative factor(s) isn’t working?
Ex. K remains low on serial BMPs despite apparently appropriate tx
○ Screen Magnesium (normal mag approx 1.5 - 2.5)
■ Hypokalemia is common in pts w/ hypomagnesemia, < K+ occurs in ~40-60% of pts w/ < Mag
■ This is primarily d/t causes of < K being the same as causes of < Mag (ex <GI absorption like poor PO intake or diarrhea, diuretic therapies, etc)
■ However there is also a “renal K+ wasting phenomenon” in setting of < Mag
(this is a specific situation where low serum and total body Mag causes low K)
● K+ secretion (meaning K+ out of the cells and into the lumen) in the proximal aspects of the collecting duct occurs via luminal potassium channels called ROMK channels
● K+ secretion through ROMK channels is mediated (inhibited) by normal intracellular Mag levels (intracellular meaning inside the cells that line the collecting duct)
● If sMag levels are very low, can lead to low intracellular Mag levels, can lead to < inhibition of the ROMK channel → more K+ out of cell and into lumen → more K+ leaving the body
● If < Mag is cause of the < K, you will never be able to correct the < K w/o correcting the < Mag
■ You don’t always have to screen Mag when screening K, but it’s advisable to always screen K levels when you find a low Mag (however it would be really strange for one to just order a mag level on someone for w/u of any issue without having already screened at least a BMP)
○ K becoming even lower despite treatment? Call nephrology !!!!
Hyperkalemia
Definitions:
● Hyperkalemia = High Potassium Levels in the Blood
● Laboratory definition of Hyperkalemia varies slightly by lab / institution, but typically is
defined as being a serum K+ of > 5.3 meq/L. (or > 5.5)
Hyperkalemia
EKGs in pts w/ hyperkalemia may show peaked T waves
● AKI… and/or other associated disease states of decreased renal secretion of K+
● Increased PO Intake leading to > GI absorption
● Decrease in shift of potassium into the cells, or cell spilling of K+ (so < intracellular K+)
Hyperkalemia:
Causes & Patho: Decrease in Renal K+ Secretion
Hyperkalemia:
Causes & Patho: Decrease in Renal K+ Secretion
● AKI:
○ An acute renal injury can lead to functional impairment of the kidney’s ability to filter the serum (at first a pt w/ AKI’s BMP may show > what?, then followed by changes in
electrolytes and other factors of the BMP)
○ Multiple mechanisms here, however AKIs in general tend to lead to hyperkalemic states, however intrarenal AKIs (and AKIs in pt’s w/ CKD) may show variable serum potassium levels
○ FYI: note that the mechanisms by which AKI may impact K levels are a little different & more multifactorial than
the mechanisms we have discussed previously regarding normal renal function and retention of sodium
● RAAS System INactivation
(opposite problem of where we were at last time):
○ Decreased RAAS system activity leads to (see physiology breakdown RAAS activity and K+ under the hypokalemia slides, cannot produce and release RENIN), with notable causative examples below:
■ Severe AKI / AKD (the AKI so severe or prolonged that it actually leads to a prolonged state of RAAS dysfunction), & CKD ← d/t the chronic global renal dysfunction
Hyperkalemia:
Causes & Patho - “Increased” K+ Availability for GI Absorption
Actual Increased Intraluminal GI K+ Levels:
○ Rarely the true primary problem as much PO K+ can just be passed in the stool, however pt’s taking hyper excessive K+ supplementation may present this way (especially if they already have other potential risk factors for developing > K+)
Normal (or High ← rare, see above^) Intraluminal GI K+ Levels:
○ The intraluminal GI K+ levels are “normal,” and the GI luminal absorption itself is still “normal,” however you have another problem elsewhere in the body causing >K+ and even the “normal” amount of GI absorption is adding fuel to the fire
■ Sometimes you need to < the K being absorbed f/ GI tract to tx even if GI tract intraluminal K levels are norm
Hyperkalemia:
Other Specific Notable Causative Factors
Aldosterone Receptor Antagonists:
○ Blocking the increased expression and activity of the Na+/K+ pump at the collecting duct leads to
less (Na+ reabsorption / K+ secretion), netting in increased serum K+ levels d/t < K+ secretion.
○ Other upstream RAAS inhibition may also cause hyperkalemia, however aldosterone receptor
antagonists are notorious for doing so given their starring role / involvement in Na+/K+ pump in the
collecting duct.
○ See next slide
Digoxin Toxicity:
○ Leads to < K+ intracellular influx
Hyperkalemia
Patiromer is a GI-active Ca++/2K+ Cation exchange resin that primarily works in the colon to keep K+ molecules from being absorbed by forcing two K+ ions to be exchanged with patiromer’s one Ca++ ion, therefor chelating the K+ ions and keeping them in the GI lumen → K+ gets passed in stool
Hits the water, calcium falls off, either sodium or potassium binds it
Stays in the GI lumen
