sodium balance pedram fatehi, md division of nephrology [email protected]
TRANSCRIPT
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Learning Objectives
• ECF volume matches total ECF sodium content.
• The kidney matches sodium excretion to sodium intake in order to maintain ECF volume.
• Recognize the volume sensors and effector mechanisms that regulate sodium excretion (i.e. regulate ECF volume).
• Explain why sodium saving mechanisms developed during evolution to prevent ECF volume reduction may be activated in disease, causing an increase in the ECF volume above normal.
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Salts are ionic compounds of cations and anions.
For our discussion, we’ll use the term “salt” to mean sodium chloride or just sodium.
Water follows Salt
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Maintaining the Internal Environment
What Goes In=
What Comes OutIntracellular
Fluid290 mOsm
Na+ 10K+ 120
Extracellular Fluid290 mOsmNa+ 140
K+ 4
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Bourque CW. Nature Reviews Neuroscience, 2008Central mechanisms of osmosensation and systemic osmoregulation
Mammals ECF~300 mOsm/kg
Non-mammals ECF(vertebrates and invertebrates)
42 – 1140 mOsm/kg~range of U Osm
(~290 mOsm/kg)
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Galapagos marine iguana has nasal salt glands to excrete excess salt.
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Terrestrial elephant finds salt deposits to replete salt deficiency.
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Intake of salty foods will prompt thirst so water (and volume) will follow.
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Maintaining the Internal Environment What Goes In = What Comes Out
High sodium diet150 mEq/day ~ 3450 mg/day
Very low sodium diet15 mEq/day~345 mg/day
Effect of abrupt changes in Na+ intake on body weight and renal Na+ excretion in a normal human. The shaded areas refer to changes in total body Na+ stores due to the difference between intake and excretion. (From Earley LE , Clinical Disorders of Fluid and Electrolyte Metabolism, 1972)
“Low Sodium Diet”<100 mEq/d ~ <2300 mg/d
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GFR ≈ 100 mL/min≈ 150 L/day
[Na] ≈ 150 mEq/L
Na filtered ≈ 150 L/day x 150 mEq/L ≈ 22,500 mEq/day
Na excreted ≈ 1 to 50 mEq/day (less than 1%)
Na+ excretion in humansis regulated by the kidney
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In nature, salt and the water that accompanies it are hard to obtain and easily lost, eg. in fever, sweat, diarrhea, blood loss; thus, evolved responses to maintain and replete ECF volume by: • Increasing sodium intake (‘salt hunger’)• Restricting sodium loss in the kidneys *
Cholera OutbreakCameroon , 2014
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a. Dehydratedb. Volume depletedc. Hypervolemicd. Hypovolemice. Edematous
How would you describe a patient with severe diarrhea from cholera?(may choose more than one)
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a. Dehydratedb. Volume depletedc. Hypervolemicd. Hypovolemice. Edematous
How would you describe a patient with severe diarrhea from cholera?(may choose more than one)
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a. Low urine sodium concentrationb. Low cardiac outputc. High stroke volumed. Fast heart ratee. Low blood pressuref. Poor tissue perfusion
Patients with very low ECF volume (ie, low salt content or salt deficiency) will have:(may choose more than one)
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a. Low urine sodium concentrationb. Low cardiac outputc. High stroke volumed. Fast heart ratee. Low blood pressuref. Poor tissue perfusion
Patients with very low ECF volume (ie, low salt content or salt deficiency) will have:(may choose more than one)
CO = HR x SV
Same for diarrhea or blood loss, both hypovolemic states.
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a. PO (oral) Waterb. IV D5W (water with 5% dextrose)c. IV NS (normal saline, Na/Cl, ~290 mOsm)d. Oral ‘Rehydration’ Therapy (Na/Cl/K/citrate/glucose, ~250 mOsm)e. IV LR (lactated ringers, Na/Cl/K/Ca/lactate, ~270 mOsm)
Reasonable options to manage severe diarrhea from cholera include: (may choose more than one)
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a. PO (oral) Waterb. IV D5W (water with 5% dextrose)c. IV NS (normal saline, Na/Cl, ~290 mOsm)d. Oral ‘Rehydration’ Therapy (Na/Cl/K/citrate/glucose, ~250 mOsm)e. IV LR (lactated ringers, Na/Cl/K/Ca/lactate, ~270 mOsm)
Reasonable options to manage severe diarrhea from cholera include: (may choose more than one)
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Intracellular Fluid
290 mOsmNa+ 10K+ 120
Extracellular Fluid290 mOsmNa+ 140
K+ 4
Hypovolemic states are managed with sodium-containing isotonic solutions, because Na+ is the major determinant of ECF volume.
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Gatorade provides (per liter): sodium 20 mEq, potassium 3 mEq
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Ernest Starling, M.D.
1866 - 1927
Starling Law of the Heart
Starling Forces of capillary filtration
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Net filtration pressure = Lp S [Δ hydraulic pressure – Δ oncotic pressure]
Lp, permeability of capillary wall; S, surface area available for filtration
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Extracellular Fluid (ECF)Volume determined by Na+ content
28 L 11 L 3 L
Plasma and interstitium are normally in equilibrium, but edema forms if altered Starling forces favor filtration into the interstitial space.
Total Body Water = 42 L (70kg x 60%)
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Kidneys and body will respond to
‘perceived’ plasma volume (not the interstitial fluid).
Intracellular Fluid
290 mOsmNa+ 10K+ 120
Extracellular Fluid290 mOsmNa+ 140
K+ 4
28 L 11 L 3 L
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(JGA)
, Aortic Arch
(Sympathetic NS)
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Rose BD, 2001
Clinical Physiology of Acid Base and Electrolyte Disorders
(Na+ and H2O)
In altered Starling forces, kidney/body
effort to restore plasma volume may
improve volume deficit somewhat, but will
also worsen interstitial edema.
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• Ring placed at thoracic inferior vena cava
• Dogs fed 75 meq / day sodium
• On Day 1 : TIVC constriction
• On Day 2 : Increased constriction
• On Day 15: Release constriction
Barger’s Caval Constriction Experiment
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Renal response to low effective
circulating volume is sodium
(volume) retention
BLOOD PRESSURE~effective circulating volume~effective tissue perfusion
RENIN
ALDOSTERONE
URINE SODIUM
PLASMA VOLUME
New Steady State
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BLOOD PRESSURE
RENIN
ALDOSTERONE
URINE SODIUM
PLASMA VOLUME
BODY WEIGHT
R ATRIAL PRESSURE
Renal response to high effective
circulating volume is sodium
(volume) excretion
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Renal response to high effective
circulating volume is sodium
(volume) excretion
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Na+ Intake: 10 mEq/day 350 mEq/day
Atrial Natriuretic Peptide
vs
Renin- Angiotensin-Aldosterone
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Case
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65M is in ED with shortness of breath; he is waiting to be seen
PMHx: HTN, DM, lipids, CAD
Extracellular fluid volume and TBW are:A. DecreasedB. NormalC. IncreasedD. Need more information
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65M is in ED with shortness of breath; he is waiting to be seen
PMHx: HTN, DM, lipids, CAD
Extracellular fluid volume and TBW are:A. DecreasedB. NormalC. IncreasedD. Need more information
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65M presents to ED with progressive dyspnea and orthopnea, ran out of diuretics x 1 wk
PMHx: HTN, DM, lipids, CAD
AF 70/palp 120 30 85%RA
Tripod position, 1 word sentences
+JVD, crackles; tachycardic, S3
Cool extremities, 3+ LE edema
Extracellular fluid (ECF) volume and TBW are:A. DecreasedB. NormalC. IncreasedD. Need more information
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65M presents to ED with progressive dyspnea and orthopnea, ran out of diuretics x 1 wk
PMHx: HTN, DM, lipids, CAD
AF 70/palp 120 30 85%RA
Tripod position, 1 word sentences
+JVD, crackles; tachycardic, S3
Cool extremities, 3+ LE edema
Extracellular fluid (ECF) volume and TBW are:A. DecreasedB. NormalC. IncreasedD. Need more information
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65M presents to ED with progressive dyspnea and orthopnea, ran out of diuretics x 1 wk
PMHx: HTN, DM, lipids, CAD
AF 70/palp 120 30 85%RA
Tripod position, 1 word sentences
+JVD, crackles; tachycardic, S3
Cool extremities, 3+ LE edema
Effective circulating volume is:A. DecreasedB. NormalC. IncreasedD. Need more information
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65M presents to ED with progressive dyspnea and orthopnea, ran out of diuretics x 1 wk
PMHx: HTN, DM, lipids, CAD
AF 70/palp 120 30 85%RA
Tripod position, 1 word sentences
+JVD, crackles; tachycardic, S3
Cool extremities, 3+ LE edema
Effective circulating volume is:A. DecreasedB. NormalC. IncreasedD. Need more information
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65M presents to ED with progressive dyspnea and orthopnea, ran out of diuretics x 1 wk
PMHx: HTN, DM, lipids, CAD
AF 70/palp 120 30 85%RA
Tripod position, 1 word sentences
+JVD, crackles; tachycardic, S3
Cool extremities, 3+ LE edema
Sympathetic nervous system and RAAS activity are:A. DecreasedB. NormalC. IncreasedD. Need more information
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65M presents to ED with progressive dyspnea and orthopnea, ran out of diuretics x 1 wk
PMHx: HTN, DM, lipids, CAD
AF 70/palp 120 30 85%RA
Tripod position, 1 word sentences
+JVD, crackles; tachycardic, S3
Cool extremities, 3+ LE edema
Sympathetic nervous system and RAAS activity are:A. DecreasedB. NormalC. IncreasedD. Need more information
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65M presents to ED with progressive dyspnea and orthopnea, ran out of diuretics x 1 wk
PMHx: HTN, DM, lipids, CAD
AF 70/palp 120 30 85%RA
Tripod position, 1 word sentences
+JVD, crackles; tachycardic, S3
Cool extremities, 3+ LE edema
Urine sodium concentration is likelyA. low, < 10 mEq/LB. high, > 50 mEq/L
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65M presents to ED with progressive dyspnea and orthopnea, ran out of diuretics x 1 wk
PMHx: HTN, DM, lipids, CAD
AF 70/palp 120 30 85%RA
Tripod position, 1 word sentences
+JVD, crackles; tachycardic, S3
Cool extremities, 3+ LE edema
Urine sodium concentration is likelyA. low, < 10 mEq/LB. high, > 50 mEq/L
![Page 43: Sodium Balance Pedram Fatehi, MD Division of Nephrology fatehi@stanford.edu](https://reader033.vdocuments.us/reader033/viewer/2022051622/5697c0031a28abf838cc37f0/html5/thumbnails/43.jpg)
Rose BD, 2001
Clinical Physiology of Acid Base and Electrolyte Disorders
(Na+ and H2O)
In altered Starling forces, kidney/body
effort to restore plasma volume may improve volume deficit
somewhat, but also worsen interstitial
edema.
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Learning Objectives
• ECF volume matches total ECF sodium content.
• The kidney matches sodium excretion to sodium intake in order to maintain ECF volume.
• Recognize the volume sensors and effector mechanisms that regulate sodium excretion (i.e. regulate ECF volume).
• Explain why sodium saving mechanisms developed during evolution to prevent ECF volume reduction may be activated in disease, causing an increase in the ECF volume above normal.
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Angiotensinogen
ACE
Renin - Angiotensin - Aldosterone
System(RAAS)
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Renin - Angiotensin - Aldosterone System(RAAS)
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ENaC
Principal Cell
Palmer BF, NEJM, 2004
Managing HyperK Caused by Inhibitors of the RAAS
Volume Regulation
• Baro-receptors
• Sympathetic NS
• RAAS
• Natriuretic Peptides
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Levin ER, et.al. NEJM, 1998
Natriuretic Peptides
Natriuretic Peptides
Physiologic effects of increased venous
return (hypervolemia)
/ ADH
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Consequence of low effective circulating volume
If we performed the IVC constriction experiment on an unsuspecting 70 kg medical student, and he ate the recommended daily intake of sodium (2400 mg) for 3 days. Approximately how much would his weight increase? (HINT, 2400 mg of Na+ = ~ 100 meq Na+)
a. 2 liters
b. 0.2 liters
c. 20 liters