Electrolytes
How each diuretic changes serum levels of electrolytes.
Here’s the three most important facts:
Loops lower everything.
Thiazides can prevent calcium kidney stones by putting less calcium into the urine.
The K-Sparers will raise the potassium.
POTASSIUM
3.5 to 5
Potassium is the most important electrolyte in clinical practice. It has a very, very narrow range that is compatible with life, because outside of that range the heart stops working. Fatal arrhythmias ensue (eg, V-tach, V-fib and Torsades). The non-cardiac symptoms aren’t very important. Not-So-Fun fact - Potassium is so deadly that it’s used in lethal injections! When thinking about the causes of Hypokalemia and Hyperkalemia, there are three main steps to consider.
Entering the body - you’d have to eat a lot of bananas to get hyperkalemia from your diet. But there are some drugs that tweak potassium absorption in the gut that can treat hyperkalemia: Patiromer and Sodium Zirconium Cyclosilicate (Kayexalate) bind K+ in the gut. Used for mild hyperkalemia treatment, and takes a day or two to kick in.
Getting shifted in and out of cells - this is the hardest part about potassium. It’s not very intuitive, and it can be hard to wrap your head around it. See diagram below. Note - insulin is used to treat life-threatening hyperkalemia (it’s given alongside glucose to neutralize the sugar-related properties of insulin).
Exiting the body - Potassium is mostly excreted through the urine. People with bad kidneys get high potassium. Most diuretics accelerate the excretion of potassium, leading to hypokalemia. The aptly named Potassium Sparing Diuretics slow down potassium excretion, leading to hyperkalemia.
The symptoms of hyper and hypokalemia are SO VAGUE. They both cause muscle cramps and weakness. Unfortunately, test makers expect you to know that.
Potassium also affects the EKG. Severe imbalances will lead to fatal arrhythmias. When you see an abnormal potassium, the first thing you do is get an EKG.
Low potassium causes flat T waves
High potassium causes tall peaked T waves that eventually grow so dominant that they take over the entire EKG, giving it a sine wave appearance.
SODIUM
135 to 145
Sodium’s job is to maintain the ECF osmolarity. Sodium and water are irrevocably linked in the body. Be aware that serum Na+ labwork is expressed as a concentration. So hypernatremia means that there isn’t much water around. And Hyponatremia means that there’s an excess of water.
In terms of clinical relevance, Hyponatremia is second only to Hyperkalemia. It’s so common, especially in the elderly and the ICU. The symptoms of Hyponatremia are strictly a consequence of shifting fluids. The clinical manifestations of hyponatremia are really only neurologic in nature secondary to cerebral edema within the confines of the cranial vault. When sodium falls outside of neurons, the neurons become comparatively full of osmoles -- which causes fluid to shift inside the cells, causing them to swell. But the brain has little real estate to expand, because it quickly runs into the skull. When the brain squishes into the skull, neurological symptoms begin. Nonspecific symptoms such as malaise or nausea are common. Headache, lethargy, confusion and obtundation may appear as sodium levels fall further. Stupor, seizures and coma eventually occur if the progression is rapid or the sodium falls below 120. Warning - correct hyponatremia slowly, or risk Central Pontine Myelinolysis!
The symptoms of Hypernatremia are similarly neurologic in nature. While the early symptoms are mild and nonspecific, such as nausea or headache, the major consequence of an extreme or rapid sodium increase is Central Pontine Myelinolysis. The Pons myelin is unusually vulnerable to changes in osmolarity. The oligodendrocytes try to synthesize osmolar proteins to adapt to an increasingly hyperosmolar environment, but to do so takes time. Nearly every nerve path in the CNS travels through the Pons at some point, so the symptoms of a lesion throughout the entire Pons are devastating (Locked In Syndrome).
UNa tests for aldosterone (inverse relationship)
Uosm tests for ADH (direct relationship)
CALCIUM
9 - 10
Calcium is *also* complicated.
Hypocalcemia is characterized by tetany, facial twitching when poked (Chvostek’s sign, aka Chvos-TAP’s sign), BP cuff induced arm contracture (Trousseau’s sign), a long QT and sometimes seizures. Hypocalcemia treatment is simple - simply administer IV calcium. Hypocalcemia is typically either caused by a surgical injury to the PT glands (during thyroidectomy) or during early CKD.
The clinical manifestations of Hypercalcemia are easy to remember using the mnemonic stones (kidney stones), bones (bone pain, pathologic fractures), groans (abdominal pain, constipation), thrones (polyuria) and psychiatric overtones (mood and psychosis problems). Other problems include a short QT, hyporeflexia and lethargy. Hypercalcemia is treated with fluids (“the solution to pollution is dilution”), plus Bisphosphonates (chronic setting) or Calcitonin (acute setting). Although it might seem reasonable to give a loop diuretic to excrete more calcium, they have fallen out of favor because they also dehydrate the patient (thus raising the concentration). There are many causes of Hypercalcemia:
Hyperparathyroidism is the most common cause of high calcium.
Primary Hyperparathyroidism is due to an adenoma that secretes PTH.
Secondary Hyperparathyroidism is not a true disease, but rather the healthy response to CKD. With CKD, the calcium is perpetually low. So all of the parathyroid glands are appropriately up-activated.
Tertiary Hyperparathyroidism is autonomous and extreme PTH secretion from the PT glands that occurs following prolonged PT gland stimulation (such as in prolonged CKD). It’s like an out-of-control train.
Cancer can cause Hypercalcemia in two ways.
Metastases travel to bone, eat it up, spill a lot of Ca and P into the blood, and the PTH reflexively drops. The use of Bisphosphonates helps to decrease bone breakdown.
A Paraneoplastic syndrome, where a tumor (usually squamous lung cancer) releases PTH-related peptide (PTHrp), which is functionally equivalent to PTH. Ca rises and P drops. The PT glands wisely decrease PTH secretion. Note that the PTH lab test doesn’t detect PTHrp.
Hypervitaminosis D is an uncommon cause. Vitamin D oral tablet overdoses are rare. But the macrophages in the middle of granulomas (eg, TB, sarcoid) release 1a-Hydroxylase, which activates Vitamin D in the PCT. The Ca and P both rise. The PCT reflexively drops.
Familial Hypercalcemic Hypocalciuria - say that five times fast. It’s asymptomatic. They have a hard time peeing out calcium. So their serum Ca rises, but only mildly (10 - 12). Very common, but of little clinical significance.
The relationship between Calcium and CKD is pretty complicated. When the kidneys fail, you lose the major source of calcium reabsorption. The bones and the gut have to pick up the pace to compensate for that loss. There are no big problems with the gut stepping up, but there are obviously a ton of problems when you dissolve your bones to gain calcium! The pattern of bone loss seen in CKD is called Renal Osteodystrophy, and it can be a real problem with CKD. Medications can help. Bisphosphonates slow down bone breakdown. Phosphate Binders (Sevelamer) decrease levels of phosphate, and since phosphate tends to gobble up calcium, the net result is an increase in calcium. Cinacalcet activates the calcium receptors on parathyroid cells, which tricks the parathyroid gland into producing less PTH, which effectively breaks the vicious cycle.
METABOLIC ALKALOSIS
pH < 7.35
The most important cause of Metabolic Alkalosis is prolonged dehydration, especially due to vomiting.
The blue highlighter is outlining the Contraction Alkalosis pathway, where dehydration makes your blood alkaline.
These can be treated with rehydration (Saline Responsive).
The disorders outside the Contraction Alkalosis pathway do not improve with IV fluids (Saline Unresponsive).
Diuretic-induced alkalosis has a variable response to saline (low yield).
METABOLIC ACIDOSIS
pH > 7.45
Metabolic Acidosis is common and deadly. Some process (outside of the lung) is turning the blood acidic. As you can imagine, there are A TON of possible causes. So we use a laboratory calculation called the Anion Gap to help us identify the cause. The Anion Gap is a bit of a tricky concept at first, but it’s actually quite simple. In the extracellular environment, there is one predominant cation (sodium), but there are many anions. The two major anions are chloride and bicarbonate. There are dozens of remaining anions, and they are difficult to individually measure, so we just lump the remaining anions into a group called the “Anion Gap.” A normal AG is roughly 10.
AG = Na - Cl - HCO3
High Anion Gap Metabolic Acidosis implies the addition of an unusual acid to the blood. I normally hate anagram mnemonics, but MUD PILES is a keeper.
Methanol (eye damage)
Uremia (Organic Acids can’t be excreted)
DKA (Diabetes)
Propylene Glycol (idk)
Isoniazid / Iron tablets
Lactic Acid (Sepsis)
Ethylene Glycol (Antifreeze → kidney damage)
Salicylic Acid (Aspirin)
Ethylene Glycol and Methanol are the toxic alcohols. They cause a high anion gap metabolic acidosis, with a high osmolar gap (evidence of some poison filling the blood). These are often found in antifreeze, and are a common route of suicide. Methanol causes eye damage, and Ethylene Glycol causes renal damage and calcium oxalate kidney stones. The treatment for both is Fomepizole, although interestingly, giving booze helps!
Non-Anion Gap Metabolic Acidosis implies the loss of bicarb. You can lose bicarb through the following routes.
You pee it out. This occurs with potassium-sparing diuretics, low Aldosterone (Addison’s) and Renal Tubular Acidosis.
You poop it out. Diarrhea is full of bicarb.
You shift it into your cells. This occurs with too much normal saline IV fluids. NS is chock full of chloride. Chloride has a negative charge. So does bicarb. Like repels like. So if you have too much chloride, it will push the bicarb into the cells.
FLUID CHANGES
