Chapter Twenty-Two: Introduction to Disorders of Osmolality

Chapter Twenty-Two: Introduction to Disorders of Osmolality

Chapter Twenty-Two: Introduction to Disorders of Osmolality
Channel Your Enthusiasm

Edited by Nayan Arora

References

  1. 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

  2. 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

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

  4. 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

  5. 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

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

  7. 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

  8. PBFluids classic: Saltiest Sodium. Dumbest Dude

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

  10. Amy’s VOG references:

    1. PMC3041494

    2. 42321668

    3. 41846300

    4. 42195166

    5. 33374011 

    6. PMC3041494

    7. PMC12884999

    8. 3102222 

    9. 42060832 

    10. 41201721 

    11. 32401639 

  11. 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