Control of Water Balance
Water is the most plentiful substance in the body, and the maintenance of volume and osmolarity of body compartments is essential for homeostasis. Changes in the extracellular fluid (ECF) alter cell volume, intracellular ionic strength, and pH, and large changes in ECF osmolality can affect the structure and function of macromolecules and ultimately the physical integrity of cells and tissues. More subtle changes in neuronal electrolyte concentrations can affect neuronal excitability and lead to altered mentation. Mammals maintain ECF at around 300 mosmol/kg. Changes in plasma osmolarity, and hence interstitial fluid osmolarity, are detected as a result of cell shrinkage in the organum vasculosum of the lamina terminalis (OVLT), a circumventricular organ located outside the blood-brain barrier in the anteroventral part of the third ventricle.1 Specialised neurons in the OVLT experience architectural changes in response to ECF osmolarity shifts, and they alter their rate of spontaneous firing. Osmosensitive neurons have projections that project into the pharyngeal and intestinal mucosae and the hepatic veins.1 These neurons can sense the osmolarity of ingested substances before plasma osmolarity changes, leading to preemptive drinking. These sensory afferents ascend to the CNS via the vagus. Thus, the magnitude and polarity of the ECF shift results in central and peripheral neural impulses conducted to the hypothalamus, posterior pituitary, and the cortex, controlling thirst, drinking, and ADH release. The main renal effect of ADH is to increase the expression of aquaporins in the collecting ducts and allow diffusion of water from the filtrate into the hypertonic medullary interstitium. However, ADH also causes efferent arteriolar constriction and is more potent than noradrenalin at doing so.2 The result of ADH secretion is an increase in GFP and a reduction in papillary blood flow.3
Thirst is stimulated both by direct OVLT sensing of increased extracellular fluid (ECF) osmolarity and indirectly by ADH release. However, the direct CNS stimulation by intracarotid infusions is less sensitive to dehydration than the ADH response, so increases in urine concentration in response to an increase in osmolarity can occur in the absence of the sensation of thirst. Likewise, during rehydration, thirst disappears before normalisation of water balance occurs.1,4 In dehydrated dogs, drinking rapidly inhibits ADH secretion long before any reduction in ECF osmolarity, which is mediated via oropharyngeal osmoreceptors.5 Thus, normalisation of plasma osmolarity is slower than might otherwise be the case, and it may be prolonged if renal concentration capacity is limited. However, although normalisation may be delayed, the onset of thirst is still very rapid and may even precede the ADH release following ingestion of a meal. Food ingestion increases plasma osmolarity, and in humans, thirst is stimulated once plasma osmolarity increases from 280 to above 295 mosmol/kg.6
As humans and rodents age, the thirst drive is less sensitive, and satiety is achieved at greater deviances from normal osmolarity than in younger individuals.7 It is not yet known if this is due to decreased sensitivity of central osmoreceptors or a reduced response of higher cortical centres to signalling from the OVLT.8 This makes old people more susceptible to dehydration.9,10 It is not known if these age-dependent changes are also present in cats or dogs; however, until proven otherwise, it is reasonable to assume they are. Factors that combine to decrease fluid intake in geriatric animals include decreased renal tubular concentration capacity, decreased mobility, and dementia. Subclinical dehydration impairs cognitive performance, memory, and depresses mood in humans, and it is likely to have similar effects in dogs and cats.11 Thus, some of the depressed mentation associated with age may be related to suboptimal hydration.
Veterinary texts have long repeated the general clinical features that indicate the degree of dehydration. Although these are widely accepted criteria, the accuracy of physical signs to estimate the degree of dehydration has been called into question. In a study of almost 200 dogs and cats presenting to a veterinary teaching hospital, the criteria were tested against the standard of increase in bodyweight following intravenous fluid therapy.12 In that study, it was shown that application of the criteria is highly inaccurate regardless of the expertise of the attending clinician. Thus, a clinical suspicion based on a combination of history and physical examination findings, and a presumption of dehydration until proven otherwise may be as sensible as the continued use of an inaccurate, if beloved scale.
Water requirements are frequently expressed as 40–60 mL/kg/24 hours. However, the true water requirements are better expressed relative to the amount of food consumed, and hence energy expenditure. Under laboratory or hospital settings, dogs and cats will naturally consume a total (voluntary plus dietary intake) of 0.1–0.2 mL:kJ. At dietary moisture contents of > 75%, even with very high fat contents, both cats and dogs will usually obtain sufficient dietary water to meet their requirements, and voluntary intake will cease. Thus, owners switching pets from moist to dry diets may be surprised by the associated increase in voluntary intake. Meal feeding results in lower total water intake than when cats are fed ad lib (Finco et al 1986). In addition, we have shown that cats allowed dry food (5% moisture) ad libitum will consume their daily requirement much quicker than when offered wet food (> 75% moisture) ad libitum. In response, cats will gradually drink their water requirements over the course of the day when fed dry food, and will thus spend the majority of the 24-hour period in a state of subclinical dehydration.
Dietary moisture has been suggested as a possible means by which the energy density can be decreased, and total energy intake decreased. Although water has a low or insignificant effect on food satiety in most mammals, food intake could be altered due to non-satiating effects. When cats were forced to lose weight during energy restriction, they regained less when offered 52% moisture food ad lib than they did when offered 12% moisture food ad lib (Cameron et al Japan 2010). However, the effect appeared to be due to increased energy expenditure rather than decreased intake. Certainly cats will ingest many more feeds when wet food is offered ad libitum than dry food. Thus, high moisture food may be associated with increased activity and improved energy expenditure. Although the magnitude of this effect has not been studied in home settings, it is unlikely to be great, since epidemiological studies conflict on the importance of dry food as a risk factor for obesity. In several studies, neither canned diets nor moist home-prepared diets have been associated with a decreased prevalence of obesity.4
Water Intake in Disease
Water is integral to the management of lower urinary tract diseases. The single most important intervention for urolithiasis and idiopathic cystitis is to reduce the urine osmolarity. Increasing dietary water intake can significantly reduce the proportion of cats with idiopathic cystitis that experience recurrence of clinical signs. Clinical signs of recurrent idiopathic cystitis recurred in 11% of cats that were fed a canned diet, whereas it recurred in 39% of cats fed a similar, dry diet designed to result in production of an acidic urine.13
Attempts to increase drinking by providing a source of running water has not yet proven to be effective. In one study of 9 household cats, there was no significant effect of water intake when cats were offered water in a fountain compared with a bowl.14 In another study, although water intake from the fountain was slightly greater, the cats' USG was no different and remained very high.15 All cats were fed dry diets. A similar study in dogs has not yet been published.
In rats with surgically created chronic kidney disease (CKD), an increase in dietary moisture reduces plasma ADH and urinary osmolality.16 Surprisingly, CKD progressed much slower, and there was a dramaticaIly reduced urinary protein excretion, reduced hypertension, kidney hypertrophy and incidence of glomerulosclerosis, and mortality. Antagonism of ADH reduces proteinuria, reduces glomerulosclerosis, and has an added benefit to ACE-inhibition in surgically induced CKD in rats.17 Thus it appears that ADH has an independent role in the progression of CKD that is related to the effect of ADH on glomerular filtration pressure and proteinuria. What needs to be established is the clinical importance of reducing ADH by maximising water intake.
The restriction of dietary sodium has long been considered an integral component of the management of CHF in dogs. In one of the few studies to directly evaluate the effects of dietary sodium restriction in 14 dogs with CHF, most echocardiographic indices improved, but plasma aldosterone, atrial natriuretic peptide, and renin were not affected.18 Plasma ADH was not measured in that study. However, ADH antagonism in dogs with CHF has been shown to decrease pulmonary capillary wedge pressure, but it had no effect on GFR, renal blood flow, or systemic arterial blood pressure.19
Wet vs. Dry Food
Both cats and dogs adjust their drinking in response to changes in dietary moisture. Studies that have evaluated the accuracy of this response have either evaluated a small number of dietary moistures or have used diets of different macronutrient composition. We have evaluated the total and voluntary intake of cats when fed the same diet but with varying water content, from 5% to 85% moisture. Between 65% and 5% moisture, cats adequately adjust voluntary intake such that the total water intake remains constant. At 75% they stop drinking, and at 85%, total intake increases and diuresis results. Between 65% and 5%, the USG remains near maximal and relatively constant. Thus, to reliably reduce urine concentration, at least 75% dietary moisture needs to be fed, and simply "adding some wet food" to a dry food diet is unlikely to have a significant effect on USG. This may explain why some studies have not shown a beneficial effect to wet diet feeding. For reducing USG, an effect may only be seen with sole feeding of a wet diet.
It is important to realise that although the total water intake may be equal, animals on dry diets are in a different physiological state to animals on wet diets. If the daily dry matter intake is consumed in a short space of time, the animal will be in a state of mild dehydration (hypohydration) until the drinking has "caught up" with the water deficit. During that time, ADH secretion will be increased, and consequently glomerular filtration pressure will be elevated relative to an animal fed a wet diet. We have shown that normal, healthy cats consuming a 5% moisture diet with ad lib access to food have an increased urine protein to creatinine ratio (UPC) than when consuming 45% or 85% moisture diets.
Although the amount of proteinuria is not "pathological," one is forced to ask if it could be deleterious in the long term. To put it in perspective, it has recently been shown that the UPC is an independent risk factor for the progression of CKD in cats.20 In that study, cats with CKD that progressed during the study period had a UPC that was significantly greater than cats with stable CKD. When the UPC of the cats is graphed against the healthy cats, it supports the hypothesis that dry diets are probably inferior in the long-term management of CKD.
Water is an essential element that is infrequently considered in nutritional studies. The management of several important and common diseases includes attempts to reduce urine concentration. The most reliable method for achieving that goal is to increase dietary moisture content, but it needs to be more than 65% moisture. Both diseased and healthy animals are not physiologically identical when consuming dry and wet diets, even with an equal daily total water intake, and there may be a cost to the chronic increased ADH secretion. Studies are sorely needed that address the independent role of dietary moisture on several diseases, most notably CKD.
References
1. Bourque CW. Central mechanisms of osmosensation and systemic osmoregulation. Nat Rev Neurosci. 2008;9:519–531.
2. Edwards RM, Trizna W, Kinter LB. Renal microvascular effects of vasopressin and vasopressin antagonists. Am J Physiol. 1989;256:F274–278.
3. Fallet RW, Ikenaga H, Bast JP, et al. Relative contributions of Ca2+ mobilization and influx in renal arteriolar contractile responses to arginine vasopressin. Am J Physiol - Renal Physiol. 2005;288:F545–551.
4. Adolph EF. Measurements of water drinking in dogs. Am J Physiol - Legacy Content. 1938;125:75–86.
5. Thrasher TN, Nistal-Herrera JF, Keil LC, et al. Satiety and inhibition of vasopressin secretion after drinking in dehydrated dogs. Am J Physiol Endocrinol Metab. 1981;240:E394–E401.
6. Gill GV, Baylis PH, Flear CT, et al. Changes in plasma solutes after food. J R Soc Med. 1985;78:1009–1013.
7. Thunhorst RL, Beltz TG, Johnson AK. Hypotension- and osmotically induced thirst in old brown Norway rats. Am J Physiol Regul Integr Comp Physiol. 2009;297:R149–157.
8. Farrell MJ, Zamarripa F, Shade R, et al. Effect of aging on regional cerebral blood flow responses associated with osmotic thirst and its satiation by water drinking: a PET study. Proc Natl Acad Sci USA. 2008;105:382–387.
9. Sheehy CM, Perry PA, Cromwell SL. Dehydration: biological considerations, age-related changes, and risk factors in older adults. Biol Res Nurs. 1999;1:30–37.
10. Kenney WL, Chiu P. Influence of age on thirst and fluid intake. Med Sci Sports Exercise. 2001;33:1524–1532.
11. Popkin BM, D'Anci KE, Rosenberg IH. Water, hydration, and health. Nutr Rev. 2010;68:439–458.
12. Hansen B, DeFrancesco T. Relationship between hydration estimate and body weight change after fluid therapy in critically ill dogs and cats. J Vet Emerg Crit Care. 2002;12:235–243.
13. Markwell PJ, Buffington CA, Chew DJ, et al. Clinical evaluation of commercially available urinary acidification diets in the management of idiopathic cystitis in cats. J Am Vet Med Assoc. 1999;214:361–365.
14. Pachel C, Neilson J. Comparison of feline water consumption between still and flowing water sources: a pilot study. J Vet Behav: Clin Appl Res. 2010;5:130–133.
15. Grant DC. Effect of water source on intake and urine concentration in healthy cats. J Feline Med Surg. 2010;12:431–434.
16. Bouby N, Bachmann S, Bichet D, et al. Effect of water intake on the progression of chronic renal failure in the 5/6 nephrectomized rat. Am J Physiol. 1990;258:F973–979.
17. Perico N, Zoja C, Corna D, et al. V1/V2 vasopressin receptor antagonism potentiates the renoprotection of renin-angiotensin system inhibition in rats with renal mass reduction. Kidney Int. 2009;76:960–967.
18. Rush JE, Freeman LM, Brown DJ, et al. Clinical, echocardiographic, and neurohormonal effects of a sodium-restricted diet in dogs with heart failure. J Vet Intern Med. 2000;14:513–520.
19. Onogawa T, Sakamoto Y, Nakamura S, et al. Effects of tolvaptan on systemic and renal hemodynamic function in dogs with congestive heart failure. Cardiovasc Drugs Ther. 2011;25 Suppl 1:S67–76.
20. Chakrabarti S, Syme HM, Elliott J. Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease. J Vet Intern Med. 2012;26:275–281.