Lecture 2: Electrolyte Abnormalities

Question 1

What is osmolality?

Answer 1

Concentration of all chemical particles found in the fluid part of the blood.

Question 2

What is the difference between osmolality and osmolarity?

Answer 2

Osmolality is the number of solute particles per 1 kg solute.

Osmolarity is the number of solute particles per 1 L of solute.

Question 3

What are colligative properties?

Answer 3

Properties of solutions that depend on the ratio of the number of solute particles to the number of solvent particles in a solution.

For ex. vapour pressure, boiling point, freezing point

Question 4

How do we measure body fluid osmolality in the clinical lab?

Answer 4

Osmometer

Question 5

What are the two types of osmometers?

Answer 5

1. Freezing point osmometers
2. Vapour pressure osmometers

Question 6

Plasma/serum osmolality is regulated between?

Answer 6

280 and 295 mmol/kg

Question 7

What are the major organs involved in water and electrolyte homeostasis? And what are their regulatory systems?

Answer 7

Brain - Thirst centre
Brain and Kidney - ADH
Kidney - RAAS
Kidney and Heart - Atrial natriuretic peptide (ANP), B-type natriuretic peptide

Question 8

What part of the body responds to an increase in osmotic pressure?

Answer 8

Osmoreceptors in hypothalamus

Question 9

When is ADH released?

Answer 9

When the hypothalamus osmoreceptors sense high osmolality (>280 mmol/kg)

Question 10

In absence of ADH urine volume is?

Answer 10

> 15 L/day

Question 11

In presence of ADH urine volume is?

Answer 11

0.5 L/day

Question 12

What is the function of ADH?

Answer 12

1. Increased vessel tone (V1 receptors)
2. Water re-absorption (V2 receptors and aquaporin 2, AQ2, channels)

Question 13

What is the function of RAAS?

Answer 13

1. Modulates blood volume and vascular tone
2. Maintain water and electrolyte homeostasis

Question 14

How do natriuretic peptides maintain water and electrolyte homeostasis?

Answer 14

1. Stretch of the atrial myocardium or ventricles causes release of ANP and BNP
2. ANP and BNP decrease sodium reabsorption from the kidney (DCT and CT)
3. They also directly inhibit aldosterone release by the adrenal.
4. Both effects result in decrease of plasma volume and sodium

Question 15

What is the formula for water excess?

Answer 15

([Na] - 140)/140 x TBW

Question 16

What is the most common electrolyte disorder?

Answer 16

Hyponatremia

Question 17

How does the body react when it detects hyponatremia?

Answer 17

1. Suppress ADH
2. Excrete dilute urine

Question 18

Why is the rapid correction of chronic hyponatremia contraindicated?

Answer 18

The correction must happen slowly to ensure that the extracellular and the intracellular osmolality is similar. This prevents the brain from shrinking.

Rapid correction will result in a higher amount of ions on the intracellular side. This will allow the fluid from the brain to enter the intracellular side, shrinking the brain.

Question 19

What are the three categories of hyponatremia and what are these categories based on?

Answer 19

1. Hypovolemia
2. Hypervolemia
3. Euvolemia

Volume

Question 20

Hypovolemia can be broken down into 2 subcategories. What are they and how do you distinguish between the two?

Answer 20

1. Renal loss
2. Non-renal loss

If urine sodium > 20, focus on renal loss

Question 21

Hypervolemia can be broken down into 2 subcategories. What are they?

Answer 21

1. End stage kidney disease
2. Congestive heart failure, cirrhosis, nephrotic syndrome

Question 22

How does congestive heart failure cause hypervolemia hyponatremia?

Answer 22

Congestive heart failure is a condition in which the heart cannot pump enough blood to meet the body’s needs.

When the heart’s blood pumping ability decreases, the kidneys cannot work as they should, which leads to an excess of fluid in the body.

Question 23

Euvolemia hyponatremia is caused by?

Answer 23

Syndrome of Inappropriate ADH (SIADH) - excess ADH

Question 24

What are the causes of SIADH?

Answer 24

1. CNS disturbance
2. Small cell carcinoma of the lung
3. Drugs
4. Exogenous hormone

Question 25

What is pseudohyponatremia caused by?

Answer 25

1. Hyperglycemia 2. Hyperlipdemia/Hyperproteinemia

Question 26

How do we measure sodium in clinical labs?

Answer 26

Ion selective electrodes (ISE)

Question 27

What is the difference between direct and indirect ISE?

Answer 27

Direct - does not dilute before measuring with ISE Indirect - dilutes before measuring with ISE

Question 28

What are the cons of using indirect ISE to measure electrolytes?

Answer 28

Affected by electrolyte exclusion effect hence, not ideal for patients with severe hyperlipidemia or hyperproteinemia

Question 29

Why would measuring with indirect ISE lead to pseudohyponatremia? Why does this not happen with direct ISE?

Answer 29

ISE measure Na ion activity, which is directly proportional to Na ion concentration in the water fraction of plasma. Direct: ISE w/o dilution therefore measures what the body regulates: Na activity Indirect: Would also work if the water fraction of a plasma sample is equal to the average ~93%, as this is what reference intervals are based on When solutes are much higher, water fraction is lower and this assumption no longer holds. Results produce low Na level that does not correlate with Na activity in plasma. This may present with pseudohyponatremia when patient is in fact hypernatremic.

Question 30

What is hypernatremia caused by and why?

Answer 30

Dehydration. Because patients forget or cannot drink (ex. coma, anesthesia, dementia)

Question 31

What are the three categories of hypernatremia and what is it based on?

Answer 31

1. Hypovolemia 2. Hypervolemia 3. Euvolemia Volume

Question 32

Hypernatremia is always associated with?

Answer 32

High plasma osmolality

Question 33

What is euvolemia hypernatremia caused by? Why?

Answer 33

Diabetes Insipidus 1. Absent/insufficient ADH production (central) 2. Absent/insufficient ADH action (nephrogenic)

Question 34

We cannot measure ADH because it is analytically challenging and overlaps in results between health and disease. What do we measure instead?

Answer 34

Copeptin

Question 35

What is copeptin?

Answer 35

C-terminal part of ADH's prohormone. It is secreted 1:1 and is more stable in vivo and ex vivo.

Question 36

The availability of epithelial sodium channel (ENaC) is controlled by?

Answer 36

Aldosterone

Question 37

Why is alkalosis associated with hypokalemia?

Answer 37

Excess sodium absorption will leave a negatively charged lumen, which will augment potassium trapping in the lumen as well as protons leading to hypokalemia and metabolic alkalosis.

Question 38

How does K homeostasis work?

Answer 38

Cells act as buffer K is constantly diffusing out of cells so Na-K ATPase pumps K in to maintain high intracellular Shift into cells: Insulin, beta adrenergics Shift outside cells: lack of insulin, acidosis (except lactic), beta adrenergic antagonists

Question 39

What are the causes of hypokalemia?

Answer 39

1. Increased loss 2. Decreased intake (rare) 3. Redistribution

Question 40

What is the treatment for hypokalemia?

Answer 40

1. Potassium replacement 2. If IV replacement: no more than 20 mmol/h 3. Long term managment in generally dietary, and oral K if necessary

Question 41

What are the clinical features of hyperkalemia?

Answer 41

Slowing of electrical conduction - ECG changes may be seen at values >6 mmol/L Final event: ventricular asystole or cardiac arrest - Arrest with ventricular fibrillation is first sign of hyperkalemia in a patient

Question 42

What are the causes of hyperkalemia?

Answer 42

1. Excessive intake 2. Decreased loss 3. Redistribution

Question 43

How does decreased loss lead to hyperkalemia?

Answer 43

1. K sparing diuretics are aldosterone antagonists or ENaC blockers 2. ACE inhibitor block angiotensin II which prevents secretion of aldosterone (Aldosterone causes Na to be absorbed and K to be excreted into the lumen by principal cells)

Question 44

What are the causes of pseudohyperkalemia?

Answer 44

1. Hemolysis 2. Delay in processing blood samples 3. Inappropriate storage temp of blood tubes 4. IV contmaintation 5. Severe leukocytosis 6. Thrombocytosis

Question 45

What are the treatments used for hyperkalemia and why?

Answer 45

In acute settings where risk of cardiac conduction abnormality: 1. Calcium gluconate because it stablizes myocardium 2. Insulin because it shifts K into cells by stimulating the activity of Na-H antiporter on cell membrane, promoting the entry of Na into cells, which leads to activation of Na-K ATPase causing an electrogenic influx of K 3. Dextrose stimulates insulin secretion causing shift of extracellular K into cells by activating cell membrane Na-K ATPase pump 4. Bicarbonate raises blood pH and shifts extracellular K into cells