Salt and water: the physiology and regulation of volume and tonicity




Common misconceptions and mistakes





  • Behaving as if humans are “brittle” with regard to volume status—namely that they transition quickly from total body volume overload to volume depletion (in a dangerous way)



  • Not resuscitating hypovolemic individuals for fear that the sodium correction will be too rapid



  • Treating hyponatremia based on the calculated Na + deficit and desired rate of increase



  • Treating hypernatremia based on the calculated free water deficit, giving half back in the first 24 hours and the remaining half over the next 24–48 hours





Volume status and tonicity





  • Life evolved in saltwater; thus humans need constant access to water and salt



  • Normal euvolemic (nonedematous) humans store ~ 10 L of saltwater in the interstitium of their bodies, with ~ 3–4 L in the interstitium of their extremities (lower extremity > upper extremity in the upright position)




    • This provides at least a 48-hour buffer against dehydration and volume depletion if water is scarce





  • The kidneys regulate volume status by adjusting glomerular filtration rate (GFR) and sodium balance, manipulating the amount of NaCl in the urine



  • The hypothalamus, pituitary (via anti-diuretic hormone [ADH] secretion and thirst), and the kidneys (by adjusting water reabsorption, responding to ADH) regulate tonicity by manipulating the amount of water or concentration of the urine



  • Maintenance of adequate circulating volume (sodium balance ) is the body’s ultimate priority




    • Therefore tonicity is sacrificed to maintain adequate volume (resulting in Hyper- and hyponatremia presentations)





  • Tonicity (practically speaking, cell size ) is dictated by water balance




    • Dehydration is a state of inadequate body water, increased tonicity, and shrunken cells, ultimately causing central nervous system (CNS) dysfunction





  • Total body volume status is dictated by sodium balance




    • hypovolemia equals total body sodium depeltion, implying = no reserve saltwater in the interstitium, no edema anticipated



    • euvolemia equals normal sodium balance , implying > 5 L of reserve saltwater in the interstitium, no edema anticipated



    • hypervolemia equals total body sodium overload , implying excessive saltwater in the interstitium, manifesting as peripheral edema



    • Volume overload is a problem of NaCl intake, not water intake




      • To illustrate, if a human eats 10 g of NaCl in a day he or she will:




        • Drink, responding to thirst as tonicity threatens to increase



        • Experience a pressure natriuresis in an attempt to prevent volume overload



        • Gain 1–2 lbs as he or she expands his or her interstitial fluid volume to the 10 + L maximum of interstitial reserve (often manifesting as sock edema)




      • Alternatively, if a human drinks 10 L of water in a day he or she will:




        • Urinate 9.5 L of a dilute urine to prevent decreased tonicity




          • Not gain weight (or manifest edema)







The Normal Homeostasis of Volume Status and Sodium Balance





  • Hypovolemia leads to a decreased circulating volume, perceived by the kidney as a decreased renal blood flow




    • Decreased renal blood flow causes a decreased GFR with subsequent activation of the renin–angiotensin–aldosterone system, leading to:




      • Decreased urine output



      • Increased sodium reabsorption to conserve salt (urine Na + < 10 mmol/L)



      • Increased ADH secretion concentrating the urine to conserve water (> 300 mOsm/kg)






  • Hypervolemia leads to an increased circulating volume perceived by the kidney as increased renal blood flow




    • Increased renal blood flow leads to an increased GFR leading to sodium spillage “a.k.a. pressure natriuresis”




      • Increased urine output



      • Sodium spillage to return volume status to normal (urine Na + > 20 mmol/L)



      • Decreased ADH secretion diluting the urine to remove water (< 100 mOsm/kg)







The normal homeostasis of tonicity and water balance





  • The hypothalamus, pituitary, and the kidney attempt to maintain tonicity homeostasis by manipulating ADH




    • Increased tonicity (ie, hypernatremia) causes increased ADH secretion, concentrating the urine



    • Decreased tonicity (ie, hyponatremia) causes decreased ADH secretion, diluting the urine





  • Inadequate water intake leads to an increased serum sodium and thus increased tonicity




    • Increased tonicity is perceived by the hypothalamus, which creates thirst and activates ADH secretion from the pituitary, leading to:




      • Increased water intake



      • Increased water reabsorption in the collecting tubule



      • Concentrated urine (> 300 mOsm/kg )






  • Water excess leads to decreased serum sodium and thus decreased tonicity




    • Decreased tonicity inhibits thirst (hypothalamus) and suppresses pituitary ADH secretion, leading to:




      • Decreased water intake



      • Decreased water reabsorption in the collecting tubule, Increasing urine output



      • Dilute urine (< 100 mOsm/kg)







The pathophysiology and evaluation of hyponatremia





  • Hyponatremia represents a state of excessive plasma water




    • This is either a result of volume depletion (in an attempt to maintain circulating volume), impaired water excretion (syndrome of inappropriate antidiuretic hormone secretion [SIADH]), or excessive water intake (overcoming the body’s ability to excrete water)



    • The most common causes of hyponatremia are:




      • Hypovolemic (gastrointestinal [GI] losses) > dilutional (occurring as a complication of volume overload) > SIADH > low sodium intake > excessive water ingestion






  • Symptoms of hyponatremia are caused by decreased tonicity




    • Decreased extracellular tonicity creates an osmotic gradient, causing water to shift into cells (intracellular tonicity, which is based on potassium, remains normal)



    • This shift of water into cells makes them swell (poorly tolerated by central neurons)




      • Causing headache, confusion, seizure, coma, and even herniation (water intoxication)



      • An acute drop in serum sodium causes:




        • Confusion (Na + ≤ 125)



        • Seizure, coma, and herniation (Na + ≤ 115)




      • A chronic drop in serum sodium is often asymptomatic until the Na + ≤ 115 mEq/L




        • When Na + drops gradually, brain cells compensate (over days or weeks) by reducing intracellular osmolality




          • This poses a danger if chronic hyponatremia is rapidly corrected



          • The previous compensatory decreased intracellular osmolality in the neurons causes them to shrink rapidly as extracellular tonicity normalizes




            • This is associated with the devastating osmotic demyelination syndrome (the disease formerly known as “central pontine myelinolysis”)









  • The first step in evaluating a low- serum sodium is establishing total body volume status (ie, edema vs no edema) ( Fig. 22.1 )




    • The next step is obtaining a urine Na + and a urine osmolality (obtain before IVF is given or expect some Na + spillage)



    • Finally, observe the urine output




    Fig. 22.1


    Flowchart showing the evaluation of hyponatremia, which initially hinges on the presence or absence of edema. The most common cause of hyponatremia is volume depletion (no edema), and the second most common cause is dilutional (generalized edema). Edematous patients with hyponatremia need no additional studies or workup (just diuresis and fluid restriction). The next aspect of the evaluation is establishing whether the urine is concentrated or dilute, distinguishing volume depletion and syndrome of inappropriate antidiuretic hormone secretion (SIADH) (concentrated urine) from very low sodium or excessive water intake (dilute urine). The next step in the evaluation of the nonedematous hyponatremic individual with a concentrated urine is ruling out volume depletion with an assessment of urine sodium. Volume-depleted individuals will have a low urine sodium. A concentrated urine with a high urine sodium suggests SIADH. Hyponatremic individuals with a dilute urine have either a very low sodium diet or excessive water intake. Individuals who have excessively consumed water will have a high urine output as anti-diuretic hormone is appropriately inhibited and their kidneys attempt to excrete the excess water.




  • Edematous patients are volume overloaded from either heart failure, cirrhosis, or renal failure




    • Hyponatremia occurring with volume overload is dilutional :




      • Heart failure or cirrhosis lead to decreased renal blood flow and decreased GFR (which directly impairs water excretion)



      • Decreased renal blood flow is erroneously perceived by the kidneys as hypovolemia, causing activation of the renin–angiotensin–aldosterone system (which causes sodium retention)



      • Angiotensin II leads to nonosmolar -mediated ADH secretion, sacrificing tonicity in an erroneous attempt to increase circulating volume



      • Together this signaling causes:




        • Low urine output from the “cardio-renal” physiology previously described



        • Concentered urine (> 300 mOsm kg) with a low Na + (< 10 mEq/L)




          • A low urine osmolality implies concomitant psychogenic polydipsia



          • A high urine Na + implies loop diuretic use or acute tubular necrosis (ATN)





      • Treat with diuresis (loop diuretics) and water restriction




    • Renal failure may impair free water excretion directly




      • Treat with loop diuretics, water restriction, and consider renal replacement therapy






  • Nonedematous patients with hyponatremia are suffering from volume depletion, impaired water excretion, very low Na + intake, or very high water intake




    • Volume depletion (suggested by hypotension, tachycardia, and low urine output )




      • Volume depletion (insufficient Na + ) leads to decreased renal blood flow




        • This is correctly perceived by the kidneys as hypovolemia, resulting in the activation of the renin–angiotensin system and leading to:




          • Nonosmolar -mediated ADH secretion, sacrificing tonicity in an appropriate attempt to increase circulating volume



          • Concentered urine (> 300 mOsm/kg)



          • Low urine output





      • Hypovolemic hyponatremia is caused by NaCl loss (either renal or extrarenal)




        • Extrarenal NaCl loss is seen with vomiting, diarrhea, and profound sweating




          • Concentrated urine, low urine sodium , and low urine output




        • Renal NaCl loss is seen with thiazide diuretics , salt-wasting syndromes, adrenal insufficiency, and distal renal tubular acidosis (RTA)





    • Euvolemic patients with hyponatremia either have impaired water excretion from inappropriate ADH secretion (ie, SIADH ) or engage in such voluminous water intake (ie, nonosmotic polydipsia) that they overcome their ability to excrete it (typically > 15 L a day)




      • Inappropriately secreted ADH causes water reabsorption from the collecting tubules, leading to:




        • An inappropriately concentrated urine (> 300 mOsm/kg)



        • A decreased serum sodium (and tonicity)



        • An increased circulating volume, increasing renal blood flow and GFR leading to sodium spillage (ie, a high urine Na + [> 20 mEq/L])




      • SIADH is common and is caused by myriad medications (eg, selective serotonin reuptake inhibitors [SSRIs]) and conditions, from pulmonary, CNS or thyroid disease to pain




    • Very low Na + intake (a.k.a. “tea and toast” or “beer potomania”)




      • Very low sodium intake causes decreased tonicity, leading to:




        • Inhibition of ADH secretion and a dilute urine (< 100 mOsm/kg)



        • Urine Na + remains low because of total body Na + depletion



        • Urine output remains normal




      • Very low sodium intake is a phenomenon of individuals who eat only “tea and toast” (ie, a diet devoid of salt) or who consume only alcohol (beer potomania)




    • Excessive water intake exists in a spectrum, from acute water intoxication to chronic psychogenic polydipsia




      • An acute ingestion of a large volume of water (5–10 L) in an hour or two, or a chronic ingestion (10–15 L day), can overcome the body’s maximum water excreting ability, causing decreased tonicity and leading to:




        • Osmotic-mediated inhibition of ADH secretion and a dilute urine (< 100 mOsm/kg)



        • Urine Na + that remains low (< 10 mEq/L) because plasma volume does not expand when ADH is inhibited (as almost all ingested water is excreted)



        • High urine output (500–1000 mL/hr) because ADH is appropriately inhibited




      • An acute, massive water ingestion is typically seen in “water-drinking contests” or psychiatric illness



      • Chronic, daily ingestion of large volumes of water (> 10 L every 24 hours) is a psychiatric illness known as psychogenic polydipsia




Sep 14, 2018 | Posted by in RESPIRATORY | Comments Off on Salt and water: the physiology and regulation of volume and tonicity
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