Electrolyte disturbances: Pathology review




Renal system

Renal and ureteral disorders
Bladder and urethral disorders
Renal system pathology review

Electrolyte disturbances: Pathology review


1 / 10 complete

USMLE® Step 1 style questions USMLE

10 questions

A 67-year-old female presents to the emergency department with nausea, vomiting, and lethargy. The patient is currently undergoing treatment for diffuse large B-cell lymphoma and last received chemotherapy two days ago. The patient’s temperature is 37.0°C (98.6°F), pulse is 121/min, respirations are 18/min, blood pressure is 92/74 mmHg, and O2 saturation is 94% on room air. On physical exam, she is pale and ill-appearing, intermittently convulsing, and has tenderness to palpation over the left flank. Laboratory findings are demonstrated below:  

 Laboratory Value  Result 
 Erythrocytes  20/hpf 
 Leukocytes  30/hpf 
 Fractional excretion of sodium (FENa  >3%  
 Urine Microscopy  + uric acid crystals 
Which of the following metabolic derangements best explains this patient's clinical presentation?


Content Reviewers:

Two people came to the Emergency Department during your shift.

One of them is 75-year-old Karen who has palpitations and muscle weakness.

Karen also has heart failure and one of the medications she’s currently on is digitalis.

The other one is 25-year-old Carmen who has tetany.

On the clinical examination, Carmen has a positive Chvostek sign.

In both these individuals, an ECG was done and levels of electrolytes were taken.

Karen’s ECG showed a wide QRS complex with peaked T waves and high levels of potassium, while Carmen’s ECG showed prolonged QT and low levels of calcium.

Okay, now let’s start talking about electrolytes and what happens when their levels are either too high or too low.

Let’s begin with potassium, which is a cation that’s mostly in the intracellular fluid, or ICF for short.

It’s essential for the normal functioning of excitable tissues, such as nerves and muscles, including the cardiac muscle, and also maintains the resting membrane potential.

So, with hyperkalemia, there’s too much potassium in the extracellular fluid or ECF.

And in order for there to be hyperkalemia, there are two possibilities.

The first is an external balance shift, like when there’s decreased potassium excretion by the kidneys, leading to increased serum potassium.

There’s also internal balance shift where potassium moves out of cells, and into the interstitium and blood.

One potential cause is hyperosmolarity.

Osmolarity reflects the number of solute particles per liter of solvent, and normally, the osmolarity of the ICF equals the osmolarity of the ECF, even though the exact composition of solutes differs.

So when there’s hyperosmolarity, this means that there’s something in the ECF that creates an osmotic force capable of dragging water from inside the cells, like glucose, for example.

As water leaves the cells, the intracellular potassium concentration increases and this creates a driving force for potassium to leave the cell, leading to a rise in extracellular potassium and hyperkalemia.

Next, acid-base disturbances also play a role in this. pH reflects the concentration of hydrogen ions and normal blood pH is about 7.4.

To maintain pH balance, hydrogen moves in and out of the cells.

In order for hydrogen to move across the cell membrane, it must be accompanied by an anion, meaning an ion with a negative charge, or it must be exchanged for another cation, like potassium.

When there’s an increase in the hydrogen ion concentration in the blood, this is called metabolic acidosis.

As a coping mechanism, hydrogen must enter the cells in exchange for potassium, which leaves the cells.

And this leads to hyperkalemia.

Another important mechanism is the sodium-potassium ATPase, which normally transports sodium out of the cell and potassium in.

Commonly tested medications like digitalis and beta blockers block the sodium-potassium ATPase, so more potassium is left outside the cell, leading to hyperkalemia.

Another medication that causes internal potassium balance shift is succinylcholine.

Succinylcholine combines with nicotinic receptors to inhibit neuromuscular transmission and produce skeletal muscle depolarization, which leads to relaxation.

With depolarization, some of the potassium gets out of the cell which in turn can cause hyperkalemia.

Finally, there’s cell lysis or cell damage.

When cells are destroyed, they release all their potassium into the ECF which naturally, leads to hyperkalemia.

Some examples of cell lysis include crush injuries, like when a piano falls on someone’s legs, or tumor lysis syndrome, which occurs when cancer treatment causes lots of tumor cells to die all at once, or rhabdomyolysis, which is the rapid destruction of skeletal muscle cells.

Alright, on to external potassium balance shifts resulting in hyperkalemia, which has to do with potassium intake and excretion.

That said, simply taking in too much potassium can lead to hyperkalemia, but this would typically arise from rapid, excessive infusion of potassium into the bloodstream, like in individuals receiving intravenous fluids.

Most other cases, have to do with the kidneys and their ability to regulate what stays in the blood and what gets excreted into the urine.

Now, an important hormone that helps regulate potassium reabsorption or secretion in the kidneys is aldosterone.

Aldosterone promotes potassium secretion by the principal cells of the distal tubule and collecting duct of the nephron.

So, in situations where somebody’s unable to produce enough aldosterone, which is called hypoaldosteronism, there’s less potassium secretion by the principal cells, and therefore more potassium is retained, leading to hyperkalemia.

Along the same lines, medications that reduce the effect of aldosterone can also cause hyperkalemia, and these include renin inhibitors, ACE inhibitors, angiotensin II receptor antagonists, selective aldosterone blockers, and potassium-sparing diuretics.

Acute and chronic kidney injury can also cause hyperkalemia because both can impair potassium excretion.

Some associated clues include oliguria or anuria, which means decreased or no urine excretion, volume overload and in advanced stages, uremia, which refers to the accumulation of uremic toxins, including urea itself.

Moving on to causes of hypokalemia, which is when there’s too little potassium in the ECF, there are, similarly, two possibilities.

The first is an external balance shift most often caused by an increase in potassium excretion in the kidneys, and the second is an internal balance shift where potassium moves into the cells, from the interstitium and blood.

One high-yield cause of internal potassium shift is hyposmolality, meaning there are too little osmotic substances, like when there’s hyponatremia, for example, then water goes back into the cells and can sometimes even drag potassium along with it, leading to hypokalemia.

However, bear in mind that alternatively, in some cases of hyperosmolarity, like in hyperglycemic hyperosmolar state, or HHS, which is a complication of diabetes mellitus, osmolarity can get so high that it leads to osmotic diuresis.

Osmotic diuresis can also drag that potassium into the urine.

And this may lead to total body potassium loss and hypokalemia.

Now, with acid-base disturbances, when there’s a primary decrease in the hydrogen concentration in the blood, this is called metabolic alkalosis.

As a coping mechanism, hydrogen must leave the cells in exchange for potassium.

More potassium gets inside the cells and this leads to hypokalemia.

Next, there are things that affect the sodium-potassium ATPase.

Specifically, beta agonists promote the activity of the sodium-potassium ATPase, leading to hypokalemia.

Next, there’s insulin which normally stimulates the sodium-potassium ATPase.

When there’s insulin deficiency, like with diabetes mellitus, there can also be hyperkalemia and when there’s too much insulin, there can be hypokalemia.

Moving on to external potassium balance shifts resulting in hypokalemia, these have to do with potassium intake or excretion.

Low potassium intake is rare since potassium is abundant in most foods.

So it typically happens in cases of anorexia, prolonged fasting, or specific types of diets.

Excess potassium excretion from the kidneys is a lot more common.

In situations where somebody produces too much aldosterone, like primary hyperaldosteronism, called Conn syndrome, there’s more potassium secretion by the principal cells, meaning more gets excreted in the urine.

Other pathological conditions that cause increased aldosterone levels include compensated heart failure and cirrhosis.

For your exams, it’s important to know that loop diuretics and thiazide diuretics also increase potassium excretion in the urine.

Alternatively, potassium can be lost through increased gastrointestinal secretions, typically due to vomiting and diarrhea, like from infections, inflammatory bowel diseases, as well as laxative abuse.

Finally, a very small amount of potassium is also lost in sweat, which could come up in your test as an individual who exercises a lot in a hot climate.

Now, once a person has hypo- or hyperkalemia, the first thing to do is an ECG.

That’s because the resting membrane potential of the cardiomyocytes depends on potassium balance.

With hyperkalemia, the main changes are wide QRS complexes and peaked T waves which put a person at risk for heart arrhythmias.

This happens because initially, the rise in potassium in the ECF makes the cell membrane less electronegative and this increases the membrane excitability, so the cardiac muscle contracts more easily, but it can’t repolarize effectively to allow another contraction.

For your tests, remember that another symptom of hyperkalemia is muscle weakness.

With hypokalemia, the main changes are flattened T waves and the appearance of U waves, which are thought to represent the repolarization of Purkinje fibers of the heart.

This happens because hypokalemia increases both the resting membrane potential and the duration of the refractory period, but has a greater effect on the refractory period, meaning it takes longer for the heart to recharge.

It also decreases conductivity, which can further lead to heart arrhythmias.

Other symptoms of hypokalemia include muscle weakness, muscle cramps, or spasms.

Let’s move on and talk about sodium, which is a cation that’s mostly in the ECF and is essential for maintaining water balance, as well as a nerve impulse conduction and muscle contraction.

So with hypernatremia, there is too much sodium in the extracellular fluid.

This can happen because a person has gained more sodium than water, or has lost more water than sodium.

Either way this increases the sodium concentration in the extracellular fluid, draws water out of the cells.

Sodium gain happens most commonly when someone in the hospital is given too much sodium intravenously too quickly.

The other possibility is salt poisoning, which is a rare scenario, but if it is seen, it’s typically in infants and young children who have been abused.

Water losses, on the other hand, is much more common, and can result in hypernatremia if the lost water is not replaced.

There are 3 possible sources: skin, gastrointestinal, and urinary losses.

Increased skin losses can occur in individuals with extensive burns, fever, exercise, and exposure to high temperatures.

Then we have the gastrointestinal losses, like vomiting, or diarrhea.

Finally, too much water can be lost through the kidneys because of osmotic diuresis.

This occurs when the osmolarity of the fluid in the renal tubules are too high and it sucks more water into the tubules which is then lost as urine.

A high yield example of this is diabetes mellitus where there’s too much glucose being filtered into the pre-urine.

Other examples include acute kidney failure, when urea builds up; or during treatment with mannitol, which is an osmotic diuretic.

When there’s hypernatremia, water will move from the ICF to the ECF until both compartments become isotonic.

This means that the cells will lose water and become dehydrated.

When neurons are affected, it can lead to symptoms such as irritability, stupor, which is when a person becomes almost unconscious and even coma.

On the other hand, true hyponatremia or low concentration of sodium in the extracellular fluid, can be caused by either losing more sodium than water, or gaining more water than sodium.

This shouldn’t be confused with false hyponatremia or pseudohyponatremia.

This is where the body water and sodium levels are normal, but there’s an excessive amount of lipids, like in hypertriglyceridemia, or proteins, like in multiple myeloma.

High levels of lipids and proteins affect the laboratory instruments that measure the sodium concentration, making the instruments say the sodium concentration is too low.

Broadly speaking, true hyponatremia can be divided into three categories based on water volume status.

The first is hypervolemic hyponatremia, where there’s an enormous increase in total body water with a less significant increase in total body sodium.

Typically, this is seen in conditions like congestive heart failure, cirrhosis, or nephrotic syndrome, which all present with edema, especially in the ankles.

The second category is hypovolemic hyponatremia where there’s a small decrease in total body water with a large decrease in total body sodium.

This can occur in conditions like diarrhea or vomiting, or in response to certain medications like diuretics.

Another more nuanced condition is cerebral salt wasting which is when an intracranial injury like meningitis disrupts the normal sympathetic nervous system stimulation of the kidneys leading to disproportionate loss of sodium and, along with it, water.

A third category is euvolemic hyponatremia, or normal volume hypovolemia, which is where there’s normal body sodium with an increase in total body water.

Ηowever, we call it “euvolemic” because there’s no edema.

Euvolemic hyponatremia can be split into cases with dilute urine and concentrated urine.

Conditions that cause dilute urine include drinking too much water called polydipsia.

The main condition that causes concentrated urine is the syndrome of inappropriate antidiuretic hormone secretion, or SIADH for short.

Certain neurological disorder can increase the secretion of ADH and this includes strokes, hemorrhages or trauma, while certain medications like mood stabilizers and antiepileptics can also increase its secretion.

It could also be excreted ectopically by tumors, and small cell lung carcinoma is the most commonly tested.

When there’s hyponatremia, water will move from the ECF in the ICF, so the cells will swell up.

When neurons are affected, it causes symptoms like nausea, malaise, stupor, coma and even seizures.

Okay, moving to calcium, which is a cation that’s mostly located in the bones and is essential for muscle contraction, enzyme activity and blood coagulation.

It also helps with releasing neurotransmitters from neurons, as well as releasing hormones from the endocrine glands.

About 1 percent of calcium is in the ECF.

Now hypercalcemia, or too much calcium in the ECF, is most commonly caused by excess parathyroid hormone secretion by the parathyroid glands, and is known as PTH-mediated hypercalcemia.

This results in increased osteoclastic bone resorption, and this is where osteoclasts break down the bone and release calcium into the blood.

Hypercalcemia can also be parathyroid hormone-related protein, or PTHrP-mediated.

PTHrP is a hormone that mimics the effect of parathyroid hormone, so it stimulates the osteoclasts.

It can be secreted by various malignancies, but for your exams, remember squamous cell carcinomas of the lung.