The maintenance of normal internal conditions in a cell or an organism is called

Water Balance in Newborns

Water balance is controlled primarily by antidiuretic hormone (ADH), which controls water absorption in the collecting duct. ADH secretion is regulated by hypothalamic osmoreceptors that monitor serum osmolarity and baroreceptors of the carotid sinus and left atrium that monitor intravascular blood volume. Stimulation of ADH secretion occurs when serum osmolarity increases to greater than 285 mOsm/kg or when effective blood volume is significantly diminished. Increases in serum osmolarity also stimulate thirst receptors in the anterior hypothalamus to promote increased water intake. Intravascular volume has a greater influence on ADH secretion than serum osmolarity. Patients with hyponatremia and concomitant volume depletion are unable to suppress ADH in response to the decrease in serum osmolarity.

At baseline, when the serum osmolarity and effective blood volume status are normal, the collecting duct is impermeable to water. In response to an increase in serum osmolarity or significant volume contraction, ADH produced in the hypothalamus binds to its receptor, arginine-vasopressin V2 receptor, located on the basolateral membrane of principal and inner medullary collecting duct cells. Receptor activation results in elevated levels of intracellular cyclic adenosine monophosphate. Downstream signaling pathways promote movement of preformed vesicles containing aquaporin 2 (AQ2) water channels to the apical surface. The presence of these water channels on the watertight apical membranes renders them permeable to water. Withdrawal of ADH stimulates endocytosis of AQ2-containing vesicles, which restores the collecting duct cells to a state of water impermeability.

This system may not be as straightforward as previously believed, however, because vasopressin V2 receptors have been shown to be expressed in nephron segments other than the collecting duct, notably the loop of Henle.42 This study and others support the emerging concept of crosstalk between the ADH/vasopressin V2 receptor system (classically considered a regulator of water homeostasis only) and the renin-angiotensin system (classically considered a sodium regulator only), which may modulate renal handling of salt and water further.

Maximal renal concentration and dilution require structural maturity, well-developed tubular transport mechanisms, and an intact hypothalamic-renal vasopressin axis. In adults and older children, decreased water intake or increased water losses activate a highly efficient renal concentrating mechanism that can produce maximally concentrated urine with an osmolarity of 1500 mOsm/kg, resulting in fluid conservation. Conversely, excessive fluid intake triggers the diluting mechanism of the kidney that can produce maximally dilute urine with an osmolarity of 50 mOsm/kg, resulting in free water excretion.

Urinary concentrating ability is diminished in neonatal kidneys, particularly those of premature infants.15,38 When challenged, term newborns can concentrate urine to an osmolarity of 800 mOsm/kg; preterm infants can concentrate urine to an osmolarity of only 600 mOsm/kg.15 This diminished urinary concentrating ability, particularly in preterm infants, may limit a neonate's ability to adjust to fluid perturbations—notably perturbations that result in increased free water losses (e.g., increased insensible water losses). Multiple factors limit renal concentrating capacity in preterm infants. Structural immaturity of the renal medulla limits sodium, chloride, and urea movement to the interstitium. Preferential blood flow through the vasa recta limits generation of a medullary gradient. Diminished urea-generated osmotic gradient in the renal medulla limits production and maintenance of the countercurrent mechanisms that are essential in producing maximally concentrated urine. Finally, tubular responsiveness to vasopressin is diminished because of decreased transcription and protein synthesis of AQ2 water channels.68

Abstract

Homeostasis denotes the maintenance, or regulation, of vital internal variables in a state of relative constancy. Automatic cellular mechanisms, neural and endocrine controls, and behavior all contribute importantly to homeostasis. Organisms that function in wider ranges of external environments tend to regulate more internal variables and to have more complex systems regulating important variables – for example, the adaptable mechanisms with which we mammals regulate body temperature allow us to function in a much wider range of external temperatures than reptiles. Most physiological homeostatic mechanisms rely on negative feedback; that is, signals related to the regulated variable are sensed and cause the system to react in a way that reduces the signals.

Intrinsic Mechanisms: Renal Autoregulation

Renal autoregulation refers to the intrinsic ability of the kidney to respond to a perturbation that elicits a vasoactive response, which alters renal vascular resistance in the direction that maintains RBF and GFR. Changes in perfusion pressure are the manipulation most commonly used to demonstrate autoregulatory efficiency. Although the efficiency with which blood flow is maintained differs from organ to organ (being most efficient in brain and kidney), all organs and tissues exhibit autoregulation. As shown inFig. 3.17, the kidney autoregulates renal blood flow over a wide range of renal perfusion pressures. Autoregulation of blood flow in response to changes in perfusion pressure requires parallel changes in resistance.

The finding that both RBF and GFR are autoregulated with a high efficiency indicates that the principal resistance change due to autoregulatory adjustments is localized to the preglomerular vasculature. Studies of single-nephron function of superficial nephrons have demonstrated that SNGFR also exhibits efficient autoregulation, as long as the tubular fluid collections do not block flow to the macula densa. Furthermore, direct measurements of glomerular pressures in the Munich-Wistar rat, which has glomeruli on the renal cortical surface that is accessible to micropuncture, have demonstrated autoregulation of glomerular pressure in response to variations in renal arterial perfusion pressure.Fig. 3.18 summarizes the effects of graded reductions in renal perfusion pressure on PGC and preglomerular (RA) and efferent arteriolar (RE) resistance.145 Graded reductions in renal perfusion pressure from 120 to 80 mm Hg result in only a modest decline in glomerular capillary blood flow, whereas a further reduction in perfusion pressure to 60 mm Hg leads to a more pronounced decline (seeFig. 3.18).

Autoregulation of glomerular capillary blood flow and PGC as perfusion pressure decreased from 120 to 80 mm Hg is the result primarily of a pronounced decrease in RA, with little or no change in RE. Over the range of renal perfusion pressures from 120 to 60 mm Hg, RE tended to increase slightly at the lower perfusion pressure. Under conditions of modest plasma volume expansion, RA declines while RE increases slightly as renal perfusion pressure is lowered so that PGC and ΔP are virtually unchanged over the entire range of renal perfusion pressures.145 The mean glomerular transcapillary hydraulic pressure difference (ΔP) exhibits almost perfect autoregulation over the entire range of perfusion pressures.145 These results indicate that autoregulation of GFR is the consequence of the autoregulation of glomerular blood flow and glomerular capillary pressure. Similar results have been obtained in other rat strains and in dogs, where proximal and distal tubular pressures and peritubular capillary pressure also demonstrated autoregulation.146

Characteristics of Homeostatic Systems

Homeostasis refers to the ability of an organism to maintain the internal environment of the body within limits that allow it to survive. Homeostasis also refers to self-regulating processes that return critical systems of the body to a set point within a narrow range of operation, consistent with survival of the organism. Homeostasis is highly developed in warm-blooded animals living on land, which must maintain body temperature, fluid balance, blood pH, and oxygen tension within rather narrow limits, while at the same time obtaining nutrition to provide the energy to maintain homeostasis. This is because maintaining homeostasis requires the expenditure of energy. Energy is used for locomotion, as the animal seeks and consumes food and water, for maintaining body temperature via the controlled release of calories from metabolism of food or fat stores, and for sustaining cell membrane function as it resorbs electrolytes in the kidney and intestine and maintains neutral blood pH. Homeostasis also refers to the body's defensive mechanisms. These include protective reflexes against such things as inhaling matter into the lungs, the vomiting reflex as a protection to expel toxic materials from the esophagus or stomach, the eye blink reflex, and the withdrawal response to hot or otherwise painful skin sensations. There is also the defense against pathogens through innate and acquired immunity, the latter of which is stimulated by acute stress via cortisol and adrenalin and inhibited by chronic stress and high levels of cortisol.3,4

Water Homeostasis

Water homeostasis is regulated by a high-gain feedback mechanism that involves the hypothalamus, neurohypophysis, and kidneys.263,264 In kidneys, the water and sodium from the glomerular filtrate are reabsorbed in tubules through water channel aquaporins (AQPs) and sodium cotransporters.265–267 The tubular reabsorption of water primarily depends on the driving force (high interstitial osmolality in the deeper medullary zones) and osmotic equilibrium of water across the tubular epithelia (high osmotic water permeability of the membrane). The large majority of glomerular filtrate is reabsorbed in the proximal tubules and descending thin limbs of the loop of Henle.266,268 The next tubular segments (thin and thick ascending limbs and distal convoluted tubules) are relatively water-impermeable.269,270 Finally, the main parts of the nephron where vasopressin-based regulation of body water homeostasis occurs are the connecting tubule and collecting duct271–273 (see alsoChapter 15). Both maximum urinary concentration and diluting capacity are decreased by aging,274 leading to a higher risk for hypernatremia and hyponatremia, respectively.

Findley has proposed an age-related dysfunction of the hypothalamic-renal axis based on clinical observations of increased vasopressin secretion in older age.275 With older age, maximal urine concentrating ability is particularly reduced.274 Compared with younger individuals, older adults have about a 50% reduced capacity to conserve water and solutes. Due to the combined effect of age-related changes in body composition, progressive microstructural changes in the kidney, and changes in plasma osmolality and fluid volume, some older adults are more prone to developing disturbances in water homeostasis. One of the major changes in body composition is an increase in total fraction of body fat by 5% to 10% and an equivalent decrease in total body water, so that an older man on average has 7 to 8 fewer liters of total body water than a young man with the same body weight.276 The obvious consequence is that in the event of acute loss, or overload of body water, a more severe change in osmolality will occur in older men. A study comparing plasma osmolality in older and younger individuals before and after a similar extent of water deprivation has confirmed this presumption.277 Alterations in water and sodium balance frequently lead to hypo- or hypernatremia associated with hypo- or hypervolemia in older adults.278,279 In addition, dysfunction in water homeostasis may also occur due to abnormal expression and trafficking of AQPs and solute transporters. For example, an animal study has shown that the AQP2 transporter involved in urine-concentrating ability is downregulated in the medulla of older rats.280 This molecular mechanism is consistent with a reduced urine-concentrating ability in older adults. Water homeostasis is also influenced by the previously described microstructural changes that occur with the aging kidney. These changes occurring with healthy aging do not pose an acute threat or have an impact while an individual is healthy. However, in the event of stress, acute disease, volume load, or dehydration, the combined effects of age-related loss of renal mass (i.e., functional reserve) and the change in body composition may cause a significant disruption in water and solute homeostasis.281,282

Body fluid homeostasis is directed at achieving stability of the two major functions of body fluids: maintenance of body osmolality within narrow limits, and maintenance of extracellular fluid and blood volume at adequate levels. Osmotic homeostasis is important to prevent large osmotic shifts of water into and out of cells, which would interfere with normal cell function, while volume homeostasis is important to allow normal cardiovascular and circulatory function. In mammals, water balance primarily controls osmotic homeostasis, and solute balance largely controls volume homeostasis. This is accomplished through finely regulated activities of the cardiovascular system, the endocrine system, and the central and peripheral nervous systems.

3 Homeostasis

Homeostasis refers to a general principle that safeguards the stability of natural and artificial systems, where stability is understood in its more classical sense of robustness against external perturbations. Homeostasis is a fundamental concept in neuropsychology, psychophysiology and neuroscience (Cannon's thesis). In the behavioral sciences, however, the concept of homeostasis is acknowledged, but it rarely fulfils a prominent role in actual analyses. A noteworthy exception is the monograph by McFarland (1971). Yet the mathematical-statistical theory of homeostasis, in particular optimal control theory of systems with feedback (e.g., Goodwin and Sin 1984), shows that homeostasis has important effects on system behavior and hence should be taken into account in statistical system modeling and analysis. Molenaar (1987) gives an application of optimal control theory to the optimization of a psychotherapeutic process.

A concise illustration is given of some of the effects of homeostasis in applied systems modeling. Homeostasis will be defined as negative feedback control (McFarland 1971). It is shown by means of a simple computer simulation that the presence of homeostasis has profound effects on measured intercorrelations between the behavior of coupled systems. Although the systems are strongly coupled, the manifest intercorrelations between their behavior approaches zero as a direct function of the strength of homeostasis. This has noteworthy implications for applied behavioral systems analysis. Consider, for instance, the long-standing research tradition investigating the biological basis (a physiological system) of personality (a behavioral system). Both systems are assumed to be coupled, but both have also to be considered as being homeostatic. The homeostatic nature of the coupled physiological and behavioral systems investigated in this research tradition therefore can be expected to yield biased measures of their coupling (i.e., intercorrelations close to zero), whereas the actual strength of this coupling may be considerable.

The illustrative simulation study is based on a simple instance of the linear state–space model in Eqn. (2). Only a single set of two coupled systems is considered, hence the subscript i can be dropped in the defining equations. To simplify matters further, it is assumed that the state s(t) is observed directly, hence the matrix H is taken to be the identity matrix and the measurement noise v(t) is absent. Denoting the unidimensional state process of system 1 (e.g., the behavioral system) by s1(t) and the unidimensional state process of system 2 (e.g., the physiological system) by s2(t), this yields:

(3a) s1t+1=f11s1t+f12s2t+w1t+1 s2t+1=f21s1t+f22s2t+w2t+1

In Eqn. (3a) f12s2(t) denotes the influence of the physiological system on the behavioral state process s1(t+1), where f12 is the strength of this coupling; f21s1(t) denotes the reverse influence of the behavioral system on the physiological state process s2(t+1).

The system Eqn. (3a) does not include homeostasis. In contrast, the following analogue of Eqn. (3a) includes homeostasis:

(3b)s1t+1=f11 s1t+f12s2t+c1s1t+w1t+1s2t+1=f21s1t+f22s2t+c2s2t+w2t+1

In Eqn. (3b) c1[s1(t)] and c2[s2(t)] denote optimal feedback functions which depend on a number of additional parameters that are not displayed explicitly. Molenaar (1987, and references therein) presents a complete description of the computation of these optimal feedback functions.

To assess the effects of homeostasis on the manifest correlation between s1(t) and s2(t), time series are generated according to Eqns. (3a) and (3b). This requires that numerical values are assigned to the system parameters in both Eqns. (3a) and (3b). For instance: f11=0.6, f12=0.4, f21=0.4, and f22=0.7. In addition, c1[s1(t)] is taken to be zero (only the physiological system 2 in (3b) includes homeostasis). It is then found that the manifest instantaneous intercorrelation between s1(t) and s2(t), as determined for a realization of T=100 time points, is 0.85 for Eqn. (3a) and 0.15 for Eqn. (3b). This shows clearly that the intercorrelation for Eqn. (3b), that is when homeostasis is present in the physiological system 2, is substantially biased towards zero and does not reflect the strength of the coupling between the two systems without homeostasis present.

The same result (substantial underestimation of the actual coupling strength by the manifest intercorrelation between coupled systems in case homeostasis is present) is found under all other possible scenarios (negative coupling between systems without homeostasis, homeostasis present in both systems, etc.). This general result also can be proven by means of mathematical-statistical methods. It is concluded that homeostasis has substantial biasing effects on manifest measures of system coupling, even in simple linear systems such as considered above.

Abstract

Homeostasis of the body’s small molecules is significant in health and disease. Homeostatic functions are in part regulated by microRNAs (miRNAs). In regenerative medicine, therapeutic miRNAs may be ideally suited to restoring the network homeostasis of small molecules, such as adenosine or glucose, in this way affecting entire regulatory networks on a more holistic level. Therapeutic miRNAs can be introduced via ex vivo gene therapies, as illustrated here for adenosine, or directly via in vivo gene therapies, an interesting area that should be explored in future applications. This chapter discusses miRNA-based experimental approaches to harness the therapeutic potential of small molecules.

Abstract

Homeostasis and allostasis are important physiological states of internal and external regulation and maintenance. The human body constantly monitors itself to create a new normal based on adapting to distress, injury, insult, diseases, and recovery. In homeostasis, a constant loop of assessment to establish the new normal is called negative feedback. The central and peripheral nervous systems are involved in the loop of assessment and reports the state of the molecules, cells, tissues, organs, and organ systems back to the brain, which responds with impulses that influence adjustments. Consequently, criteria of what constitutes normal functioning is provided through a very narrow range of values that can be interpreted through results of diagnostic testing.

Homeostasis is the maintenance by an animal of a relatively constant state, which in turn increases efficiency of physiological processes. From a behavioral perspective, homeostasis can be as simple as moving back and forth between sun and shade to keep body temperature constant. Assessment and behavioral response to internal state, such as hunger, thirst, and searching for mates are all homeostatic processes, many of which are regulated by feedback loops. Adjusting time investment in activities—time budgeting—allows animals to accomplish the various tasks required for survival. Biological clocks help animals to adjust their homeostatic activity. Topics such as sleep, fear, and pain fall within the general realm of this topic as well. Within a species, animals may vary in their responses to a particular set of circumstances; this variation is an expression of personality, or behavioral syndrome. Oftentimes, behavioral syndrome is expressed as a shy to bold continuum, with some animals in a population behaving more boldly than others. Homeostasis is the key to understanding why an animal performs a specific behavior at a given time.