IN OUT Na Na Determinants of TBW Age Fat 20muscle 80 80 infants 70 infants 60 A fter Puberty E xtra C ellular 3340 Intra C ellular 6067 The cell membranes are ID: 1010601
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1. Salt & Water homeostasisINOUTNa+Na+
2. Determinants of TBWAge;Fat (20%)/muscle (80%);80% infants70% infants60% After PubertyExtraCellular (33-40%)IntraCellular(60-67%)The cell membranes are:freely permeable to water not permeable electrolytes different solute composition of the two compartments: extracellular fluid: sodium salts (chloride and bicarbonate major anions); intracellular fluid: potassium salts (large macromolecular organic phosphates main anions)Rule of thumbTBW is classically estimated as:60% of body weight in men;50% of body weight in women deducting 5% for elderly patients.
3. Rule of thumbTBW is classically estimated as:60% of body weight in men;50% of body weight in women deducting 5% for elderly patients. Absolute weight-based rules of estimation apply only to a select population of healthy individualsDerived regression equations better predict TBW in a broader range of subjects have been developed to account for anthropomorphic data such as age, gender, ethnicity, weight, and height.
4. Intracellular fluid volume (cytosol - water contained within cells):about 2/3 of TBW;Varies with age;determined by the absolute amounts of sodium and water that are present in the ECF.Regulation:The maintenance of fluid homeostasis in each of these compartments is dependent on the excretion of fluids and the concentration of electrolytes that generate osmotic pressure. This process of passive regulation of osmotic pressure is known as osmoregulation.The solute concentration difference across the membrane gives rise to a gradient that facilitates the movement of a solvent (usually water in our body) until attaining equilibrium. The tendency of a solution to draw water in through the semipermeable membrane is the osmotic pressure.Determinants of TBWAge;Fat/muscle;ExtraCellular (33-40%)IntraCellular(60-67%)Selectively permeable membrane Osmosis Jiatong Chen et al StatPearls 2021. Physiology, Osmoregulation and ExcretionPic and Pec represent intracellular and extracellular hydrostatic pressures, respectively, and IIic and IIec represent osmotic pressures
5. Body Fluid Dynamics: Back to the Future Bhave et al JASN 2011
6. Human aquaporins: regulators of transcellular water flow Day et al Biochimica et Biophysica Acta 1840 (2014): 1492-1506
7. Extracellular fluid volume:about 1/3 of TBW;Varies with age;determined by the absolute amounts of sodium and water that are present in the ECF.Regulation (1):The ECF volume is regulated by alterations in urinary sodium excretion that are primarily mediated by variations in the activity of what:promotes sodium retention: renin-angiotensin-aldosterone and sympathetic nervous systems;promotes sodium excretion: natriuretic peptides;Regulation (2):The hormonal changes that regulate the ECF volume are mediated by sensors in:the renal afferent glomerular arterioles (for renin), carotid sinus (for sympathetic activity), atria and ventricles (for natriuretic peptides) that respond to changes in pressure, not volume.Determinants of TBWAge;Fat/muscle;ExtraCellular (33-40%)IntraCellular(60-67%)
8. To maintain homeostasis, the excretion of water and electrolytes must match an individual’s intake…Studies have shown that sodium intake of 10 times the normal amount has relatively small changes in extracellular fluid volume and plasma sodium concentration as a result of renal compensationJiatong Chen et al StatPearls 2021. Physiology, Osmoregulation and ExcretionAdequate organ perfusion,proper thermoregulation,excretion of toxic wasteelectrolyte balance.INNa+Na+OSMOREGULATIONElectrolytes excretionWater free excretion
9. Jiatong Chen et al StatPearls 2021. Physiology, Osmoregulation and ExcretionKey mechanisms contributing to osmoregulationSympathetic regulation: Strong activation of the renal sympathetic nerves can constrict the renal arterioles and decrease renal blood flow and GFR, leading to increased fluid retention.Autoregulation: Renal autoregulation helps maintain a relatively consistent GFR and establish delicate control of the excretion of water and solutes. In particular, the tubuloglomerular feedback mechanism of the macula densa serves to ensure steady delivery of sodium chloride to the distal tubule, consequently reducing spurious fluctuations in renal salt excretion.Hormonal regulation:Angiotensin II has numerous direct effects on tubular function, including decreased medullary blood flow in the vasa recta, tubule hypertrophy, relative efferent arteriolar constriction leading to the maintenance (or rise) in GFR, and compensatory sodium absorption to maintain fluid balance. Angiotensin II also stimulates the production and release of aldosterone and ADH, both important hormonal contributors to electrolyte and fluid balance.Atrial natriuretic peptide gets released in response to elevated atrial pressure. It acts to increase GFR and sodium filtration as well as inhibit sodium uptake, leading to volume loss at the distal convoluted tubule.Aldosterone has effects on the distal tubule and collecting duct by increasing sodium uptake and potassium excretion into the urine; this is mediated via upregulation of basolateral Na+/K+ pumps, epithelial sodium channels, amongst other mechanisms, resulting in net fluid retention. ADH serves a primary function to increase solute-free water reabsorption in the nephrons (less water excretion) to bring down body fluid hypertonicity; this is induced by the insertion of water channels (aquaporin-2) on the apical membrane of the collecting duct.
10. ???? HoweverDeterminants of TBW(60% body weight)ExtraCellular (one third)IntraCellular(two third)26% (about 3/4 of ECF) interstitial7% (about 1/5 of ECF) intravascular fluid (Plasma)80 kg adult man48 l TBW16 l ECF32 l ICF12.8 l interstitial fluid3.2 l intravascular fluid (plasma)
11. Body Fluid Dynamics: Back to the Future Bhave et al JASN 2011 ECF is subdivided into five subcompartments: plasma volume; interstitial and lymph fluid; dense connective tissue and bone;transcellular fluid within body cavities such as the pleural space, cerebrospinal fluid system, peritoneal cavity, and recirculating ductal secretions from the gastrointestinal tract; adipose tissueSex, age, obesity modify distribution of the ECF compartment!
12. Body Fluid Dynamics: Back to the Future Bhave et al JASN 2011
13. Body Fluid Dynamics: Back to the Future Bhave et al JASN 2011
14. Body Fluid Dynamics: Back to the Future Bhave et al JASN 2011
15. Titze Kindey Int 2013Starling forces and flid exchange between compartmentsTraditional view:Hydraulic pressureOncotic pressure ?Role Interstititium?Role of lymphatic system?Role of immune cells/fibroblast?
16. Body Fluid Dynamics: Back to the Future Bhave et al JASN 2011 Traditional viewDynamic view
17. Body Fluid Dynamics: Back to the Future Bhave et al JASN 2011
18. ….are the kidneys the only player? ….kidney independent reservoir of electrolytes and water? The role of the interstitium!
19. Sodium and water handling during hemodialysis: new pathophysiologic insights and management approaches for improving outcomes in end-stage kidney disease Canaud et al Kidney Int 2019; 95:296-309It has been established that total body sodium includes 3 main components: the traditional model of osmotically active sodium presenting in the total extracellular space, and implicated in the control of extracellular fluid volume, compartmental fluid composition, and hemodynamic responses;a slowly exchangeable pool of sodium located in the bones; a recently described component stored in tissue (skin and muscle interstitium), representing so-called “water-free tissue” storageLocal hypertonicitySystemic hypertonicity
20. Body Fluid Dynamics: Back to the Future Bhave et al JASN 2011 When the mechanism of excess Na+ storage across tissues is broadly surveyed, a hypothetical framework comes into view. Relatively cellular tissues such as muscle exchange Na+ for K+ or other intracellular osmolytes as their high cell mass relative to interstitial space provide a large osmole depot for transcellular exchange. Relatively acellular connective tissues have minimal intracellular osmoles at their disposal and alternatively depend on osmotically active storage with interstitial glycosaminoglycans or osmotically inactive storage with mineral matrix.
21. The interstitium conducts extrarenal storage of sodium and represents a third compartment essential for extracellular volume and blood pressure homeostasis Wing et al Acta Physiologica 2018; 222:e13006 Stewart Front Vet Sci 2020; 7:609583Modulation of intertitium:Cells (fibroblast, resident immune cells)Collagen compositionGlycosamminoglycans Charge of the interstitium
22. Organ protection by SGLT2 inhibitors role of metabolic energy and water conservationMarton Nat Rev Nephrol 2021
23. Organ protection by SGLT2 inhibitors role of metabolic energy and water conservationMarton Nat Rev Nephrol 2021Hypothesized key organ-specific metabolic changes in patients on SGLT2 inhibitor therapy
24. Organ protection by SGLT2 inhibitors role of metabolic energy and water conservationMarton Nat Rev Nephrol 2021
25. Sodium and water handling during hemodialysis: new pathophysiologic insights and management approaches for improving outcomes in end-stage kidney disease Canaud et al Kidney Int 2019; 95:296-309
26. Sodium and water handling during hemodialysis: new pathophysiologic insights and management approaches for improving outcomes in end-stage kidney disease Canaud et al Kidney Int 2019; 95:296-309Achieving Na+ balancing control in HD:Na+ assessment via NaMRIModern biosensors for continous monitoring of Na mass trasnfer
27. Take home messagesLocal hypertonicitySystemic hypertonicityCanaud et al Kidney Int 2019; 95:296-309