When potassium needs to be given intravenously, it must be given slowly.

Potassium is irritating
to the vein and is usually administered at a maximal rate of 10 mEq per hour. Moreover, infusing
potassium too quickly can cause heart irritation and promote potentially dangerous rhythms such
as ventricular tachycardia.

A potassium bolus run too fast can cause an MI that would kill the patient. Potassium can also
extravasate and cause necrosis to the surrounding tissue.
Even giving potassium at the prescribed rate, via a pump, causes a lot of irritation to the vein and
patients c/o pain at the site.

Your hospital should have a policy on running IV Potassium. Call Pharmacy and have them print you
a copy so you can show your preceptor.

Her patient got lucky this time, believe me.

Potassium is an electrolyte, 98% of which is intracellular. The 2% remaining outside the cell has great
implications for cells that generate action potentials. Doctors prescribe potassium for patients when
there is insufficient potassium, called hypokalemia, in the blood. The potassium can be given orally,
which is the safest route; or it can be given intravenously, in which case there are strict rules and
hospital protocols on the rate at which it is given.

The usual intravenous dose is 10–20 mEq per hour and it is given slowly since it takes time for the
electrolyte to equilibrate into the cells. When used in state-sanctioned lethal injection, bolus
potassium injection affects the electrical conduction of heart muscle. Elevated potassium,
or hyperkalemia, causes the resting electrical potential of the heart muscle cells to be lower than
normal (less negative). Without this negative resting potential, cardiac cells cannot repolarize
(prepare for their next contraction).

Depolarizing the muscle cell inhibits its ability to fire by reducing the available number of sodium
channels (they are placed in an inactivated state). ECG changes include faster repolarization (peaked
T-waves), PR interval prolongation, widening of the QRS, and eventual sine-wave formation
and asystole. Cases of patients dying from hyperkalemia (usually secondary to renal failure) are well
known in the medical community, where patients have been known to die very rapidly, having
previously seemed to be normal.
Increased extracellular potassium levels result in depolarization of the membrane potentials of
cells due to the increase in the equilibrium potential of potassium. This depolarization opens
some voltage-gated sodium channels, but also increases the inactivation at the same time. Since
depolarization due to concentration change is slow, it never generates an action potential by
itself instead, it results in accommodation. Above a certain level of potassium the depolarization
inactivates sodium channels, opens potassium channels, thus the cells become refractory. This
leads to the impairment of neuromuscular, cardiac, and gastrointestinal organ systems. Of most
concern is the impairment of cardiac conduction which can result in ventricular
fibrillation or asystole

1
How does hyperglycemia cause excessive urine production? To
answer this, we need to look at the renal handling of glucose.
Being a small molecule, glucose is freely filtered. The glucose
that is filtered is then completely reabsorbed in the proximal
tubule, by the mechanism shown in the figure at the right.
Under normal circumstances, 100% of the glucose that is
filtered is reabsorbed. Glucose reabsorption involves transport
proteins (specifically, sodium-glucose cotransporters) that
require specific binding. As shown in the figure below,
hyperglycemia causes such a high filtered load of glucose, that it
exceeds the capacity of the kidney tubules to reabsorb it. (Filtered load is the amount filtered, and is
calculated by multiplying the plasma concentration by the GFR). The transport proteins become
saturated, and the result is that glucose ends up in the urine. Glucose is a solute that draws water
into the urine by osmosis. Thus, hyperglycemia causes a diabetic to produce a high volume of
glucose-containing urine.

2
REGULATION OF BODY POTASSIUM

K+ is the major intracellular ion. Only 2% is in the ECF at a concentration of only 4 mEq/L.
K is taken up by all cells via the Na-K ATPase pump. It is one of the most permeable ion
across cell membranes and exits the cells mostly via K channels (and in some cells via K-H
exchange or via K-Cl cotransport).

1. Roles of K

K is the major ion determining the resting membrane electrical potential, which in turn, limits
and opposes K efflux. Thus changes in K concentrations (particularly in the ECF) have
marked effects on cell excitability (heart, brain, nerve,muscle).

K is the mayor intracellular osmotically active cation and participates in cell (intracellular)
volume regulation (exits with Cl when cells swell).

A constant cell K concentration is critical for enzyme activities and for cell division and
growth.

Intracellular K participates in acid base regulation through exchange for extracellular H and
by influencing the rate of renal ammonium production.

Regulation of extracellular K is by tissue buffering (uptake of K excess) and by slower renal

excretion.

2. Cellular K buffering

When K is added to the ECF, most of the added K is taken up by the cells, reducing the ECF
K+ increase. Similarly, if K is lost from the ECF, some K+ leaves the cells, reducing the ECF
K decline.

Buffering of ECF K through cell K uptake is impaired in the absence of aldosterone or of

insulin or of catecholamines.

Cell K exit to the ECF increases when osmolarity increases (as in diabetes mellitus) and in
metabolic acidosis, when it is exchanged for ECF protons (H+). When cells die, they release
their very high K content to the ECF.

3. Renal regulation of Potassium

In normal function, renal K excretion balances most of the K intake (about 1.5 mEq/Kg per
day). The kidneys excrete about 15 % of the filtered K load of 10 mEq/Kg per day.

Along the proximal tubule the K concentration remains nearly equal to that in plasma. Since
the PCT reabsorbs about 2/3 of the filtrate water, it also reabsorbs about 2/3 (66%) of the
filtered K. This reabsorption is mostly passive and is driven by the positive tubule electrical
potential present along the S2 and S3 segments and by paracellular solvent drag.

3
Along the descending limb of the loop of Henle, K is secreted into the tubule lumen from the
interstitium. Along the thick ascending limb, K is reabsorbed via Na-K-2 Cl cotransport. In
the loop, there is net K reabsorption of 25% of the filtered K.

Along the distal tubule and collecting ducts, there is net secretion of K which is stimulated by
aldosterone and when there is dietary K excess. Secretion decreases and becomes net
reabsorption in K deficiency. Regulation of renal K excretion is in the CD and is mostly by
changes in the rate of K secretion.

In the CD, K secretion is by the principal cells (via luminal K channels and basolateral Na-K
ATPase) and K reabsorption is by the alpha intercalated cells via a luminal H-K ATPase.

K secretion from principal cells into the CD lumen is enhanced by luminal and cellular
determinants:

Luminal determinants that stimulate K secretion are increases in tubule urine flow (which
reduces the intratubular K concentration), the delivery of sodium to the CD, and the delivery
of poorly reabsorbed anions (other than Cl) to the CD. Na delivery followed by its
reabsorption increases K secretion by increasing the lumen negative electrical potential and
by stimulating the activity of the Na-K ATPase which results in enhanced accumulation of K
in the cells. The presence in the CD of poorly reabsorbed anions (SO42-, excess of HCO3, beta
hydroxybutyrate, or HPO42-)enhances the negativity of the CD lumen, favoring K secretion.

Cellular determinants of K secretion are the activity and abundance of K channels at the
luminal cell membrane and of Na-K ATPase at the basolateral membrane. Both of these are
enhanced primarily by aldosterone, and also by ADH (by decreasing urine flow, ADH
reduces K secretion, but by increasing luminal permeability, ADH promotes it) and by
dietary K excess. K deficiency is associated with increased activity and expression of luminal
H-K ATPase in the alpha intercalated cells of the CD, which act to promote reabsorption of K
from the lumen.

NA

Regulation of Na+ Balance

Na+ and Extracellular Fluid Volume
Na+ Reabsorption along the Nephron

Regulation of Na+ Reabsorption

 Renin-Angiotensin-Aldosterone System
 Juxtaglomerular Apparatus
 Atrial Natriuretic Peptide

4
High anion gap[edit]
Main article: High anion gap metabolic acidosis

The anion gap is affected by changes in unmeasured ions. A high anion gap indicates acidosis.
In uncontrolled diabetes, there is an increase in ketoacids due to metabolism ofketones.
Ketoacids are unmeasured anions, so there is a resulting increase in the anion gap. In these
conditions, bicarbonate concentrations decrease by acting as a buffer against the increased
presence of acids (as a result of the underlying condition). The bicarbonate is consumed by the
unmeasured cation(H+) (via its action as a buffer) resulting in a high anion gap.

 Lactic acidosis
 Ketoacidosis
 Diabetic ketoacidosis
 Alcohol abuse

 Toxins:
 Methanol
 Ethylene glycol
 Propylene glycol
 Lactic acid
 Uremia
 Aspirin
 Phenformin
 Iron
 Isoniazid
 Cyanide, coupled with elevated venous oxygenation

 Renal failure, causes high anion gap acidosis by decreased acid excretion and decreased
HCO3− reabsorption. Accumulation of sulfates, phosphates, urate, and hippurateaccounts for
the high anion gap.

Note: the classic mnemonic physicians use to remember the causes of anion gap metabolic
acidosis is MUDPILES (methanol, uremia, diabetic ketoacidosis, propylene glycol,isoniazid, lactic
acidosis, ethylene glycol, salicylates). Variations include MUDPILERS with an "R" for
rhabdomyolysis; MUDPALES with the "A" representing alcoholic ketoacidosis. However, these
are outdated and include low yield items that are no longer in use. Historically, the "P" in these
mnemonics stood for paraldehyde. As paraldehyde is no longer used medically, the "P" often
refers to propylene glycol. Additionally, three “new” organic anion-gap-generating acids and acid
precursors have been recognized since the initial acronym was created. D-lactic acidosis occurs
in patients with short bowel syndromes; 5-oxoproline (or pyroglutamic acid) is associated with
chronic acetaminophen use by malnourished women; and propylene glycol infusions, often used
as the solvent for several parenteral medications including lorazepam, phenobarbital, and others
is metabolised to D-lactate and L-lactate. These changes and additions required an update to the
mnemonic. Thus, GOLD MARK has been suggested for use by nephrologists in the 21st
century.[12] This acronym represents glycols (ethylene glycol and propylene glycol), oxoproline, L-

5
lactate, D-lactate, methanol, aspirin, renal failure, and ketoacidosis. Finally, another mnemonic
CUTE DIMPLES includes cyanide, toluene, and a second "E" for ethanol (alcoholic ketoacidosis)
(cyanide, uremia, toluene, ethanol, diabetic ketoacidosis,isoniazid, methanol, propylene
glycol, lactic acidosis, ethylene glycol, salicylates). Perhaps the easiest mnemonic is KULT:
ketones, uremia, lactate and toxins, because these are the most common causes of a high anion
gap metabolic acidosis (HAGMA). The mnemonic for the (rare, in comparison) toxins is ACE
GIFTs: aspirin, cyanide, ethanolic ketosis, glycols (ethylene and propylene), isoniazid, ferric iron,
toluene.

Normal anion gap[edit]

Main article: Normal anion gap acidosis

In patients with a normal anion gap the drop in HCO3− is the primary pathology. Since there is
only one other major buffering anion, it must be compensated for almost completely by an
increase in Cl−. This is therefore also known as hyperchloremic acidosis.

The HCO3− lost is replaced by a chloride anion, and thus there is a normal anion gap.

 Gastrointestinal loss of HCO3− (i.e., diarrhea) (note: vomiting causes hypochloraemic

alkalosis)
 Renal loss of HCO3− (i.e., proximal renal tubular acidosis(RTA) also known as type 2 RTA)
 Renal dysfunction (i.e., distal renal tubular acidosis also known as type 1 RTA)
 Renal Hypoaldosterone (i.e., renal tubular acidosis also known as type IV RTA)
characterized by elevated serum potassium.
There are three types.
1. Low Renin may be due to diabetic nephropathy or NSAIDS (and others causes).
2. Low aldosterone may be due to adrenal disorders or ACE inhibitors.
3. Low response to aldosterone maybe due to potassium sparing diuretics, Bactrim, or
diabetes (and other causes).[13]

 Ingestions
 Ammonium chloride and acetazolamide, ifosfamide.
 Hyperalimentation fluids (i.e. total parenteral nutrition)
 Some cases of ketoacidosis, particularly during rehydration with Na+ containing IV
solutions.
 Alcohol (such as ethanol) can cause a high anion gap acidosis in some patients, but a
mixed picture in others due to concurrent metabolic alkalosis.
 Mineralocorticoid deficiency (Addison's disease)

Note: a useful mnemonic to remember this is FUSEDCARS (fistula (pancreatic), uretero-

enterostomy, saline administration, endocrine (hyperparathyroidism), diarrhea, carbonic
anhydrase inhibitors (acetazolamide), ammonium chloride, renal tubular acidosis,
spironolactone)

Low anion gap[edit]

6
A low anion gap is frequently caused by hypoalbuminemia. Albumin is a negatively charged
protein and its loss from the serum results in the retention of other negatively charged ions
such as chloride and bicarbonate. As bicarbonate and chloride anions are used to calculate
the anion gap, there is a subsequent decrease in the gap.

In hypoalbuminaemia the normal anion gap is decreased with 2.5 to 3 mmol/L per 1 g/dL
decrease in serum albumin.[14] Common conditions that reduce serum albumin in the clinical
setting are hemorrhage, nephrotic syndrome, intestinal obstruction and liver cirrhosis.

The anion gap is sometimes reduced in multiple myeloma, where there is an increase in
plasma IgG (paraproteinaemia).[15]

Corrections can be made for hypoalbuminemia to give an accurate anion gap.[16]