Physiology Note - Water and Sodium Homeostasis

 

Contributed by Srikant Behera,

AIIMS  Bhubaneswar

Water and Sodium Homeostasis

Introduction: Disorders of serum sodium and water balance are the commonest electrolyte disorders encountered in intensive care unit (ICU) setting. It is associated with higher morbidity and mortality among ICU patient. So, a detail understanding of water and sodium homeostasis are paramount importance for critical care physicians. Water and sodium homeostasis refers to the complex physiological mechanisms that regulate the balance between the total body water and the concentration of sodium in the extracellular fluid. Maintaining this balance is essential because even small deviations can impair cellular function, and overall cardiovascular and neurological health.

Body Water Distribution: Water is an important biological solvent and it provides an ideal environment for biochemical reactions. Total body water (TBW) accounts for about 50–60% of body weight (less in elderly and obese individuals). It is distributed as: Intracellular fluid (ICF): ~2/3 of TBW, Extracellular fluid (ECF): ~1/3 of TBW. Interstitial (IS) fluid accounts for 75% of ECF whereas Plasma accounts for 25% of ECF (figure 1). The main barrier between intravascular and interstitial fluid is the capillary endothelium and between the interstitial and intracellular fluid compartment is cell membrane.  Water moves freely across these membranes; so, its distribution depends largely on osmotic gradients, primarily created by sodium in the ECF as sodium is the major extracellular cation.

                        

                            Figure 1: Body Water Distribution

Sodium and Water Balance: The average dietary sodium intake is 100–200 mEq/day. The kidneys excrete excess sodium and maintain a stable sodium balance, adjusting excretion based on physiological needs. Water intake occurs via drinking and food, and metabolic water production; whereas water is lost through urine, sweat, feces, insensible losses (lungs and skin), etc. Sodium is the primary determinant of ECF volume; so, the changes in sodium content results in changes in ECF volume. Sodium content regulates volume, while water balance regulates sodium concentration.

Mechanisms of Water and Sodium Homeostasis

Sodium (Na+) is restricted mainly to extracellular fluid (ECF), and is a major determinant of its osmolality and volume. There are various physiological mechanisms that regulate sodium and water balance in the human body. These processes achieve acute and chronic sodium regulation by simultaneous or sequential changes. The fraction of ECF volume in the vascular system partly determines pressure on both arterial and venous circulations. Adequate cardiac output and mean arterial blood pressure are major determinants of Na+ and water homeostasis.

Volume regulation: Volume regulation is mediated by sensors in carotid sinus, aortic arch, juxtaglomerular apparatus, atria. These sensors regulate RAAS, SNS, ADH, and natriuretic peptides to maintain stable circulating volume and blood pressure. Osmoregulation: Plasma osmolarity is normally maintained at 275–295 mOsm/kg. The osmoreceptors in the hypothalamus detect small changes in osmolarity, adjust ADH release to regulate water excretion, Thirst mechanism stimulates water intake when osmolarity rises (Figure 2). So, ADH and thirst work simultaneously to correct imbalances.

                                

                                    Figure 2: Water and Sodium Homeostasis by Thirst Mechanism

REGULATION OF WATER AND SODIUM HOMEOSTASIS

Role of Cardiovascular System:

Body fluids protect circulatory blood volume by altering Na+ and water balance.  Plasma and IS Fluid are continuously interchanged because of starling forces (hydrostatic and osmotic) operating at the capillary level. Dynamically, the balance between these two opposite forces determines distribution of water between the interstitial fluid and plasma. Single layer capillary endothelial cells permit free movement of water and other solutes. Outward movement of fluid from capillaries at the arteriolar end occurs at one liter per hour because hydrostatic forces are greater than osmotic forces. About 85% of this filtered fluid is returned directly at the venule end as hydrostatic pressure falls. The remaining almost 15% (nearly 3.5 to 4.0 L per day) returns to the circulation via the lymphatic system.

Effective Circulatory Blood Volume (ECBV): It is related to ECF volume, systemic blood pressure and cardiac output. If ECBV is low and tissue perfusion inadequate, various Na+ and water retaining mechanisms are activated in order to maintain the ECBV. The reduction in ECBV may be due to a pump problem (e.g. cardiac failure) or disturbances in starling forces (e.g. cardiac failure, nephrotic syndrome)

Role of Renal and Endocrine System:

The kidney has two important functions for Na+ and water balance: filtration and reabsorption. Normally filtration is autoregulated, so the reabsorptive mechanisms adjust to variable input and output. Every minute 125 mL (180 L/day) of filtrate containing 17 mmoLs of Na+ (daily 25,000 mmoLs) enters the proximal tubule (PT); 99% is reabsorbed and 1% (1.8 L) excreted as urine. Depending on the demands from the body for conservation or excretion, urine volume can vary from 0.5 to 25 L and urine osmolality can vary from 40-1400 mosm/L. Reabsorption of filtered Na+ load varies quantitatively and qualitatively in the different parts of the nephron, majority (65%) being reabsorbed from the PT. Water diffuses passively from all parts of the nephron except the LOH. The hydrostatic and colloid osmotic forces of the renal interstitium and peritubular capillaries influence renal tubular reabsorption. Rapid and large volume Na+ reabsorption in the early part of the PT is favoured by high oncotic pressures in the peritubular capillaries (PTC).

Renin–Angiotensin–Aldosterone System (RAAS): RAAS is essential for regulating water and sodium homeostasis. Renin is released from modified fenestrated and granular endothelial cells in the afferent arteriole in response to low renal perfusion pressure from decrease in actual or effective blood volume, decreased sodium chloride delivery to macula densa, sympathetic stimulation (β1 receptors), etc. Renin converts angiotensinogen → angiotensin I, and angiotensin I is converted to angiotensin II (AT II) by angiotensin converting enzyme. AT II has variable effects on water and sodium homeostasis as it increases GFR by EA vasoconstriction, and decreases GFR by reducing the filtration surface area due to mesangial cell contraction.  It increases Na+ reabsorption in the PT by stimulating Na+-H+ exchanger. Also, AT II is a potent stimulus for synthesis of aldosterone. Low oral Na+ intake or plasma Na+ level increases the synthesis and release of aldosterone. Aldosterone is an endogenous mineralocorticoid steroid hormone from the adrenal cortex. It is a potent hormone for Na+ reabsorption, acts on distal tubules and collecting ducts, play a pivotal role in regulating renal tubular sodium reabsorption, causes sodium reabsorption, and water retention secondary to Na⁺ resulting in ECF volume expansion. Both angiotensin II and aldosterone increase the quantity of ECF sodium, but also increase the ECF volume by increasing reabsorption of water.

Anti Diuretic Hormone (ADH): ADH is synthesized in the hypothalamus and released from the posterior pituitary in stimulus to increased plasma osmolarity, decreased blood volume or blood pressure, stress, pain, nausea, etc. It acts on V2 receptors in collecting ducts, resulting in increased water reabsorption. So, it concentrates urine, and returns plasma osmolarity toward normal. In short, if osmolarity rises, ADH increases water retention; and if osmolarity falls, ADH secretion is suppressed causing dilute urine. In certain clinical conditions, increased ADH release may occur despite normal ECF osmolality. This causes water retention and dilutional hyponatremia.

Atrial Natriuretic Peptides (ANP): It is released in response to atrial or ventricular stretch (volume overload). ANP is a counter-regulatory mechanism to the renin angiotensin system. It also decreases sympathetic tone, dilate afferent arteriole and increases GFR.  It Inhibits sodium reabsorption in renal tubules, promotes natriuresis and diuresis, and thus reduces the ECF volume.  ANP acts as an endogenous diuretic, and has a specific role in volume overload conditions.

Cortisol: Cortisol is an endogenous glucocorticoid steroid hormone released from the adrenal cortex has a role in sodium reabsorption from the renal distal tubules and collecting. So, adrenal insufficiency with glucocorticoid deficiency results in decreased effective circulating volume.

Thyroid Function: There is no clear mechanistic association between thyroid hormones and sodium or water balance regulation to explain the observed association between hypothyroidism and low serum sodium concentrations. However, it is proposed that fluid retention, impaired cardiac and renal function, may lead to decreased effective circulating volume.

Gastrointestinal System

For a 70 kg adult daily Na+ intake is 100-150 mmols and daily oral fluid intake is 1.5-2.5 L. Approximately 8 L fluids containing contain 1200-1400 mmol of Na+ are produced and secreted by various parts of GIT. Out of these 8L, 6 to 6.5 L is reabsorbed in the small intestine and the remainder passes to the large intestine where further absorption occurs. Only 100- 200 mL of fluid and 4-5 mmol of Na+ are excreted in the stool.

Miscellaneous

Sympathetic Nervous System (SNS): SNS is activated during hypovolemia, leading to stimulation of renin release and renal vasoconstriction which results in decreased sodium excretion and enhanced sodium reabsorption in proximal tubules leading to sodium and water conservation.

Prostaglandins (PGs): PGs (e.g. PGE2) have an important role in maintaining renal blood flow particularly under conditions of stress. Their production is increased in response to hypotension and renal ischemia. They have also been shown to influence water and Na+ excretion.

Nitric Oxide (NO:  NO is synthesized in vascular endothelium as well as tubular cells of the kidney. It has been shown to inhibit Na+ reabsorption in the CD and opposes the renal vasoconstrictor effects of AT II.

Sweating and respiration: Water is also lost insensibly through the skin and lungs (approximately 400 mL via each) but partly compensated by water gain due to metabolic processes (nearly 400 mL).

Clinical Significance

Dysnatraemia: It is the term used to describe serum sodium level outside the normal physiological range. Depending on serum sodium concentration, it can be hyponatremia (serum sodium concentration <135 mmol/L) or hypernatremia (serum sodium concentration>145 mmol/L). Dysnatraemia happens from dysregulation of body water and sodium homeostasis. Mechanisms for dysnatraemia onset can include a combination of neuroendocrine dysfunction in the setting of severe critical illness, primary CNS injury (i.e., TBI or SAH), chronic comorbidities, renal impairment, or drug effects.

Hypovolemia/Hypervolemia: Hypovolemia occurs due to sodium and water loss from haemorrhage, diarrhoea/vomiting, diuretics, burns, etc. whereas hypervolemia is caused by conditions like heart failure, excess IV fluids, kidney failure, cirrhosis of liver, etc.

Summary

Water and sodium homeostasis is a tightly controlled system regulated through multiple pathways, including RAAS, ADH, natriuretic peptides, and sympathetic activity. ADH affects water only, while aldosterone affects sodium. These mechanisms work in harmony to maintain plasma osmolarity, circulating volume, and blood pressure. Disturbances in these systems lead to clinically significant disorders such as hyponatremia, hypernatremia, hypovolemia, and hypervolemia. Disorders of sodium concentration usually reflect water imbalance, not sodium imbalance. Sodium content determines ECF volume. Water balance determines sodium concentration. Understanding these regulatory pathways is essential for diagnosing and managing fluid-electrolyte disorders in clinical practice.

Recommended Reading

1.     Raman V, Ramanan M, Edwards F, Laupland KB. A Contemporary Narrative Review of Sodium Homeostasis Mechanisms, Dysnatraemia, and the Clinical Relevance in Adult Critical Illness. Journal of Clinical Medicine. 2025; 14(19):6914. https://doi.org/10.3390/jcm14196914

2.     Patel, Santosh. Sodium Balance-An Integrated Physiological Model and Novel Approach. Saudi Journal of Kidney Diseases and Transplantation 20(4):p 560-569, Jul–Aug 2009.

3.     Mariavittoria D'Acierno, Robert A Fenton, Ewout J Hoorn, The biology of water homeostasis, Nephrology Dialysis Transplantation, Volume 40, Issue 4, April 2025, Pages 632–640, https://doi.org/10.1093/ndt/gfae235

4.     Guillaumin J, DiBartola S. Disorders of sodium and water homeostasis. In: Clinical small animal internal medicine. John Wiley & Sons; 2020. p. 1067–1077.