PRINCIPALI PATOLOGIE DELL’EQUILIBRIO ELETTROLITICO ED IDRICO
Il mantenimento dell’omeostasi è un processo continuo, in cui la quantità di acqua e di sali presenti nell’organismo cambia istante per istante in relazione all’assunzione di una bevanda o ad un episodio di sudorazione.
L’organismo si avvale di una risposta integrata per correggere alterazioni del bilancio idrico e salino; tuttavia esistono due patologie in cui tale equilibrio viene meno: la disidratazione e la iperidratazione. In base alla concentrazione extracellulare di sodio è possibile suddividerle in ipotonica, isotonica e ipertonica
DISIDRATAZIONE
E’ una patologia molto frequente che si verifica quando avviene una perdita di acqua superiore al 6% dei valori normali. I sintomi più importanti sono: sete intensa, cute secca e poco elastica, labbra screpolate, urine scarse e concentrate ed anche rapida perdita di peso.
Generalmente la perdita di acqua avviene con perdita di elettroliti. Si distinguono tre tipi di disidratazione: grave quando la perdita di liquidi è superiore all’8-10% del peso corporeo. I sintomi sono molto gravi. La possibilità di sopravvivenza è intorno al 50%. La reidratazione per via infusionale è indispensabile; media quando la perdita di liquidi va dal 5% all’8% del peso corporeo; ed infine lieve quando la perdita di liquidi è inferiore al 5% del peso corporeo.
La disidratazione è:
Ipotonica: deficit di fluidi associato a mancanza di sodio. La bassa osmolarità dello spazio extracellulare produce una riduzione del volume extracellulare.
Isotonica: carenza di sodio e di acqua. Il volume extracellulare è ridotto e l’osmolarità del siero e il volume intracellulare sono normali.
Ipertonica: carenza di acqua ed elevata osmolarità del siero e riduzione del volume extracellulare. Come risultato della diffusione di acqua, il volume intracellulare è ridotto e l’osmolarità è aumentata.
IPERIDRATAZIONE
Ipotonica: eccesso di acqua con elevato volume sia intracellulare che extracellulare. L’osmolarità del siero e dello spazio intracellulare è ridotta
Isotonica: eccesso di acqua e di sodio. L’osmolarità del siero è normale, il volume extracellulare è elevato e quello intracellulare è normale.
Ipertonica: sodio e fluidi in eccesso. L’osmolarità del siero e il volume extracellulare sono aumentati. Come risultato della diffusione, il volume intracellualre è ridotto e la sua osmolarità è elevata.
I maratoneti ad esempio, sono molto suscettibili a questa patologia nel caso in cui durante la maratona bevano solo acqua. Anche se il sudore è relativamente ipotonico rispetto ai liquidi corporei, i maratoneti sudano molto e per lunghi periodi, facendo sì che il loro livello di sodio diminuisca quando essi consumano una grossa quantità di fluidi per attenuare la sete.
Il ricambio di fluidi potrebbe non contenere sodio sufficiente per ripristinare ciò che è andato perso e questa situazione rappresenta un alto rischio per i maratoneti.
Central regulation of sodium appetite
Geerling JC, Loewy AD. – Exp Physiol. 2008 Feb;93 (2):177-209.
Polyuria
Involvement of prostaglandin E2, cAMP, and vasopressin in lithium-induced polyuria. 1988
Am J Physiol. 1988 Jun;254(6 Pt 2):R863-9.
Sugawara M, Hashimoto K, Ota Z.
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Abstract
The involvement of prostaglandin E2 (PGE2), adenosine 3',5'-cyclic monophosphate (cAMP), and vasopressin in lithium-induced polyuria was investigated in rats. Administration of LiCl (4 mmol/kg body wt) for 7 days induced a marked polyuria with a significant excretion of urinary PGE2. Administration of indomethacin (IND, 5 mg/kg body wt) for 4 days to lithium-induced diabetes insipidus (LiDI) rats diminished urine volume by 80% and urinary PGE2 by 85%. The in vitro data of the intact rat kidney showed that lithium stimulated arginine vasopressin (AVP)-induced PGE2 production and suggested that PGE2 suppressed cAMP synthesis in rat renal medulla. The AVP-induced PGE2 synthesis was greater and the AVP-stimulated cAMP production lower in the LiDI rat kidney in vitro. Interference of the vasopressin-associated cAMP system and the increased PGE2 synthesis in the kidney may be involved in the development of LiDI. The reduced cAMP production in the LiDI rat kidney might be partly due to the increased PGE2 synthesis. In LiDI rats plasma vasopressin increased, whereas AVP concentration in the hypothalamus and the neurohypophysis significantly decreased. It is postulated that lithium stimulates vasopressin release from the central nervous system and that elevated plasma vasopressin potentiates PGE2 production in the kidney synergistically with lithium.
The Clinical Physiology of Water Metabolism
Part II: Renal Mechanisms for Urinary Concentration; Diabetes Insipidus 1979
The renal reabsorption of water independent of solute is the result of the coordinated function of the collecting duct and the ascending limb of the loop of Henle. The unique juxtaposition of the ascending and descending portions of the loop of Henle and of the vasa recta permits the function of a counter-current multiplier system in which water is removed from the tubular lumen and reabsorbed into the circulation. The driving force for reabsorption is the osmotic gradient in the renal medulla which is dependent, in part, on chloride (followed by sodium) pumping from the thick ascending loop of Henle. Urea trapping is also thought to play an important role in the generation of a hypertonic medullary interstitium. Arginine vasopressin (AVP) acts by binding to receptors on the cell membrane and activating adenylate cyclase. This, inturn, results in the intracellular accumulation of cyclic adenosine monophosphate (AMP) which in some fashion abruptly increases the water permeability of the luminal membrane of cells in the collecting duct. As a consequence, water flows along an osmotic gradient out of the tubular lumen into the medullary interstitium.
Diabetes insipidus is the clinical condition associated with either a deficiency of or a resistance to AVP. Central diabetes insipidus is due to diminished release of AVP following damage to either the neurosecretory nuclei or the pituitary stalk. Possible causes include idiopathic, familial, trauma, tumor, infection or vascular lesions. Patients present with polyuria, usually beginning over a period of a few days. The diagnosis is made by showing that urinary concentration is impaired after water restriction but that there is a good response to exogenous vasopressin therapy. Nephrogenic diabetes insipidus can be identified by a patient's lack of response to AVP. Nephrogenic diabetes insipidus is caused by a familial defect, although milder forms can be acquired as a result of various forms of renal disease. Central diabetes insipidus is eminently responsive to replacement therapy, particularly with dDAVP, a long lasting analogue of AVP. Nephrogenic diabetes insipidus is best treated with a combination of thiazide diuretics as well as a diet low in sodium and protein.
Huntington Disease
Lesser sensitivity to hypo-osmotic stress??
Brain Res Bull. 2008 May 15;76(1-2):70-9. Epub 2008 Jan 9.
Increased thirst and drinking in Huntington's disease and the R6/2 mouse., 2008
Wood NI, Goodman AO, van der Burg JM, Gazeau V, Brundin P, Björkqvist M, Petersén A, Tabrizi SJ, Barker RA, Morton AJ.
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
Abstract
While Huntington's disease (HD) is a condition that primarily involves the basal ganglia, there is evidence to suggest that the hypothalamus is also affected. Because the osmoreceptors regulating thirst are situated in the circumventricular region of the hypothalamus, we were interested in whether altered thirst is a part of the HD phenotype. We used the LABORAS behavioural monitoring system and water consumption to show that drinking behaviour was abnormal in R6/2 mice. By 10 weeks of age, R6/2 mice spent significantly more time drinking and drank a greater volume than their wild-type (WT) littermates. The numbers of immunoreactive vasopressin neurons in the paraventricular nucleus (PVN) of the hypothalamus in R6/2 mice were significantly decreased from 8 weeks of age, suggesting that the change in drinking behaviour may be the result of hypothalamic dysfunction. We gave a xerostomia (dry mouth) questionnaire to HD patients and control subjects, and also measured their urine osmolality and serum vasopressin. The mean total xerostomia score was significantly higher in HD patients than in controls, indicating greater thirst in HD patients. Urine osmolality was unaffected in HD patients up to clinical stage III, and none of the patients had diabetes. However, serum vasopressin was increased, suggesting a dysregulation in the control of hypothalamic vasopressin release. A dry mouth can affect taste, mastication and swallowing, all of which may contribute to the significant weight loss seen in both HD patients and R6/2 mice, as can dehydration. We suggest that increased thirst may be an important and clinically relevant biomarker for the study of disease progression in HD.
J Physiol Pharmacol. 2008 Dec;59 Suppl 8:109-16.
Vasopressin in vascular regulation and water homeostasis in the brain., 2008
Kozniewska E, Romaniuk K.
Laboratory of Experimental Neurosurgery, Department of Neurosurgery, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. ewak@cmdik.pan.pl
Abstract
It is well known that vasopressin participates in the regulation of the cardiovascular system, water electrolyte balance and many functions of the central nervous system. Receptors for vasopressin are widely distributed throughout the brain. They are present in neurons, in astrocytes and their perivascular processes, in endothelial and smooth muscle cells of blood vessels and in choroid plexus. Such a location suggests that vasopressin may participate in the regulation of vascular resistance in cerebral circulation and water homeostasis in the brain. Present review of the data published on this subject suggests that endogenous vasopressin is involved in brain pathology rather than in physiological regulations. Numerous studies have shown increased release of vasopressin and expression of vasopressin receptors in the brain following ischemia, trauma or subarachnoid hemorrhage in patients and in animal models of these diseases. Moreover, it has been demonstrated that antagonists of vasopressin V(1a) receptors are able to alleviate brain edema and spastic changes in blood vessels after subarachnoid hemorrhage. Vasopressin is also implicated in brain edema and in impairment of cerebral vasculature in hypo-osmotic states. The discussed results suggest that vasopressin V(1a) receptors antagonists may be a useful tool for the treatment of some states associated with cerebrovascular pathology.
Acta Neuropathol. 2010 Dec;120(6):777-88. Epub 2010 Sep 7.
Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses., 2010
Gabery S, Murphy K, Schultz K, Loy CT, McCusker E, Kirik D, Halliday G, Petersén A.
Department of Experimental Medical Sciences, Lund University, Sweden.
Abstract
Huntington disease (HD) is a fatal neurodegenerative disorder caused by expansion of a CAG repeat in the HD gene. Degeneration concentrating in the basal ganglia has been thought to account for the characteristic psychiatric symptoms, cognitive decline and motor dysfunction. However, the homeostatic control of emotions and metabolism are disturbed early in HD, and focused studies have identified a loss of orexin (hypocretin) neurons in the lateral hypothalamus in HD patients. There has been limited assessment of other hypothalamic cell populations that may be involved. In this study, we quantified the neuropeptide-expressing hypothalamic neurons known to regulate metabolism and emotion in patients with HD compared to healthy controls using unbiased stereological methods. We confirmed the loss of orexin-expressing neurons in HD and revealed substantial differences in the peptide expression of other neuronal populations in the same patients. Both oxytocin- and vasopressin-expressing neurons were decreased by 45 and 24% , respectively, while the number of cocaine- and amphetamine-regulated transcript (CART)-expressing neurons was increased by 30%. The increased expression of CART in the hypothalamus is consistent with a previous study showing increased CART levels in cerebrospinal fluid from HD patients. There was no difference in the numbers of neuropeptide Y-expressing neurons. These results show significant and specific alterations in the peptide expression of hypothalamic neurons known to regulate metabolism and emotion. They may be important in the development of psychiatric symptoms and metabolic disturbances in HD, and may provide potential targets for therapeutic interventions.
The Brain Renin-Angiotensin System Controls Divergent Efferent Mechanisms to Regulate Fluid and Energy Balance, 2010
Arginine vasopressin (AVP) neurons in the hypothalamus are osmosensory neurons that respond to increased or decreased plasma osmolarity by releasing more or less AVP, respectively, from their axon terminals.
