References

This is the famous Edelman equation from JCI in 1958 by Isodore Edelman! Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water (not to be confused by Isildur House of Isildur - Tolkien Gateway

Joel mentioned his slide deck on Edelman: https://pbfluids.com/wp-content/uploads/2023/04/QN_III-The-Edelman-Equation-full-lecture-from-2020-07-30.pdf

This is an excellent review (with great figures) on Osmotic homeostasis by Danziger and Zeidel in CJASN 

Joel and JC mentioned the work from Joseph Verbalis on hyponatremia- this is an excellent review that includes population data from NHANES plus striking images of the osteopenic bones in hyponatremic rats! Check this out! Hyponatremia‐induced osteoporosis - Verbalis - 2010 - Journal of Bone and Mineral Research - Wiley Online Library

Joel and JC mentioned “reference 2” from the chapter by Kleeman and others on diuretic induced hyponatremia which invoked hypokalemia as an important player: Diuretic-Induced Hyponatremia | Annals of Internal Medicine

We couldn't help flirting with diarrhea a little Secretory diarrhoea: mechanisms and emerging therapies - PMC

We talked about cravings for those with salt losses and here’s one example Gitelman syndrome in a South African family presenting with hypokalaemia and unusual food cravings - PMC

PBFluids classic: Saltiest Sodium. Dumbest Dude

Volume Depletion versus Dehydration: How Understanding the Difference Can Guide Therapy here’s one of many articles that argues for choosing language wisely. 

Amy’s VOG references:

PMC3041494

42321668

41846300

42195166

33374011 

PMC3041494

PMC12884999

3102222 

42060832 

41201721 

32401639 

Link to Goljian Physiology Spotify! Episode 2 is Fluid and Hemodynamics: https://open.spotify.com/show/1uD6090Kkg01b4zr2ouNiM?si=e7f609e0d9634840

Outline: Chapter 22

Introduction to Disorders of Osmolality

Hyponatremia and hypernatremia are common clinical problems

Reflect abnormalities of water balance that may or may not be accompanied by changes in Na balance

Water Distribution and Osmotic Pressure

TBW makes up 60% of lean body weight in men

50% of lean body weight in women

60% intracellular

40% extracellular

One-fifth of extracellular water is in the intravascular space

Breakdown

70 kg man

TBW = 42 L

25 L intracellular

17 L extracellular

3 L of the 17 L is intravascular

Osmotic forces determine the distribution of water

Each compartment has one major solute that holds water within the compartment

Na → extracellular compartment

K → intracellular compartment

Plasma proteins → plasma space

Urea is an ineffective osmole

Physiologic Effects of Changes in Plasma Osmolality

Figure 22-1

Na pulls water from the intracellular compartment

Increases extracellular volume

Decreases intracellular volume

Even though Na is locked in the extracellular compartment

Administering Na increases osmolality everywhere by changing water distribution

Increases extracellular volume

Decreases intracellular volume

Example

Adding 210 mEq Na to 17 L ECF would mathematically increase concentration by 12.5 mEq/L (210/17)

Actually only raises serum Na by ~5

Water moves from cells

Na remains trapped in ECF

Ultimately diluted in TBW

210/42 L = 5 mEq/L

Adding water

Expands both compartments

Dilutes osmolality in both compartments

Giving isotonic saline

Expands extracellular compartment only

Does not change intracellular volume

Changes in osmolality and intracellular volume

Responsible for symptoms of hypo- and hypernatremia

In these examples

Extracellular volume is increased

Sodium concentration may be high, low, or normal

Meaning of Plasma Sodium Concentration

Na, glucose, and urea are the primary extracellular osmoles

Gives osmolality calculation

Under normal conditions

Glucose and BUN contribute <10 mOsm/L

Therefore

Plasma osmolality ≈ 2 × plasma Na

Hypernatremia represents hyperosmolality

Hyponatremia usually reflects hypo-osmolality

Exception: hyperglycemia

Plasma Sodium Concentration and Total Body Osmolality

If plasma Na reflects plasma osmolality

And plasma osmolality is in equilibrium with total body osmolality

Then plasma Na reflects total body osmolality

Since

Total body osmolality = (ECF solutes + ICF solutes) / TBW

And

Na and K (plus accompanying anions) are the major extracellular and intracellular solutes

Then

Plasma Na ≈ (Na + K) / TBW

Figure 22-2

Key Edelman figure

Loss of potassium

K moves out of cells

To maintain electroneutrality

Na enters cells

Lowers serum Na

Or Cl leaves with K

Lowers intracellular osmolality

Water moves from cells to ECF

Dilutes serum Na

Or extracellular H dissociates from buffers and enters cells

Combines with intracellular buffers

No net movement of solute

Water still leaves cells

Serum Na diluted

Suggests K loss is responsible for much diuretic-induced hyponatremia (Ref 2)

DKA example

0.45% NS with 40 mEq KCl is insufficient to correct hyperosmolality

Hyponatremia and Hypernatremia

Can result from alterations in

Na

K

Water

Usually due to water abnormalities

Exception

Thiazides

Loss of both Na and K contributes

Toxicity of K prevents excess K from producing hypernatremia

Diarrhea

Isosmotic to plasma

Ionic composition varies

Secretory diarrhea (cholera)

Na + K approximately equals plasma Na

Causes volume depletion

Does not cause hypernatremia

Osmotic diarrhea

Fecal Na + K between 30 and 110

Nonreabsorbed solutes account for remainder

Causes hypernatremia

Diarrheal illness

Often causes fever

Increases insensible losses

Also stimulates ADH and thirst

Usually water balance remains near normal

Infants commonly become hypernatremic

Regulation of Plasma Osmolality

Daily variation in water intake and loss alters plasma osmolality

Water intake

Drinking

Water content of food

Water of oxidation

Carbohydrates metabolized to CO2 and H2O

Water retention lowers plasma osmolality

Water loss

Urine

Feces

Skin

Respiratory tract

Water loss raises plasma osmolality

Water intake and excretion are tightly regulated

Osmoreceptors in hypothalamus

After water load

Plasma osmolality falls

ADH release inhibited

Urinary water loss increases

Hyperosmolality

Stimulates thirst

Stimulates ADH

Increases water intake

Decreases water loss

Regulation disrupted by

Neurologic disorders

Hypothalamus

Posterior pituitary

Renal disorders

Impaired concentrating or diluting ability

Nonosmotic stimuli

Volume depletion

Osmoregulation versus Volume Regulation

Table 22-2

Plasma osmolality

Ratio of solute to water

Extracellular volume

Determined by absolute amount of Na and water

Two examples

Exercising on a hot day

Loss of dilute sweat

↑ Plasma osmolality (Na)

↓ Extracellular volume

SIADH

↓ Plasma osmolality (Na)

↑ Extracellular volume

Nice exercise at bottom of page 691

Isotonic saline

Does not change osmolality

Hypothalamus not activated

Increased volume suppresses renin

Increases ANP

Water load

Inhibits ADH

Produces dilute urine

Rapid restoration of volume

Only transient volume expansion

Little effect on renin or ANP

NaCl without water

Expands extracellular volume

Stimulates renal NaCl loss

Also stimulates thirst and ADH

Produces small volume of concentrated urine

Similar to intake

Volume Depletion versus Dehydration

They are not synonyms

Urine Osmolality and Specific Gravity

Relation Between Intake and Output

Simply comparing ins and outs is inadequate

Composition of fluids may differ markedly

Replacing urinary losses with free water

Produces hyponatremia