Sodium pathophysiology

Research in this area advanced in the 1970 s as several groups reported the isolation of potent toxins from P. brevis cell cultures (2-7). To date, the structures of at least eight active neurotoxins have been elucidated (PbTx-1 through PbTx-8) (8). Early studies of toxic fractions indicated diverse pathophysiological effects in vivo as well as in a number of nerve and muscle tissue preparations (reviewed in 9-11). The site of action of two major brevetoxins, PbTx-2 and PbTx-3, has been shown to be the voltage-sensitive sodium channel (8,12). These compounds bind to a specific receptor site on the channel complex where they cause persistent activation, increased Na flux, and subsequent depolarization of excitable cells at resting... 

FIGURE 13-1. Electrolyte transport in the airway epithelial cell. Ca, calcium cAMP, cyclic-3, 5 -adenosine monophosphate Cl, chloride Na, sodium K potassium. (From Milavetz G, Smith JJ. Cystic fibrosis. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 592, with permission.)... 

The potent antidiuretic hormone AVP orchestrates the regulation of free water absorption, body fluid osmolality, cell contraction, blood volume, and blood pressure through stimulation of three G-protein-coupled receptor subtypes Vi-vascular types a and b, V2-renal, and V3-pituitary. Increased AVP secretion is the trademark of several pathophysiological disorders, including heart failure, impaired renal function, liver cirrhosis, and SIADH. As a consequence, these patients experience excess water retention or inadequate free-water excretion, which results in the dilution of sodium concentrations, frequently manifesting as clinical hyponatremia (serum sodium concentration <135mmol/L). This electrolyte imbalance increases mortality rates by 60-fold. Selective antagonism of the AVP V2 receptor promotes water... 

HYPONATREMIA (SERUM SODIUM LESS THAN 135 MEQ/L) Pathophysiology... 

Prishchepa LA, Burdyga TV, Kosterin SA 1996 Two components of sodium azide-insensitive Mg2+, ATP-dependent Ca2+ transport in ureteral smooth muscle membrane structures (translated from Russian). Biokhimiia 61 1250—1256 Rose JG, Gillenwater JY 1973 Pathophysiology of ureteral obstruction. Am J Physiol 225 830-837... 

Apart from the pathophysiological condition of the animal, the mode of drug application may also significantly influence the pharmacokinetic profile of a drug (48, 49). For example, drug residues may persist at the injection site for prolonged periods of time (2). In a study in which various sulfonamides and trimethoprim were injected intramuscularly into swine, detectable residues were found at most sites 6 days after the injection, and with the sulfonamides at 30 days in almost half of the animals (50). Other drugs such as dihydrostreptomycin persist for up to 60 days, while positive residues of chloramphenicol are found at 7 days postinjection. Sodium and procaine penicillin, neomycin, tylosin, and oxytetracycline residues have also been determined at 24 h or more postinjection (51). 

Pathophysiology In HF patients, the levels of aldosterone are elevated, even in the presence of ACE inhibitors or angiotensin-receptor blockers (34,35). Aldosterone has detrimental effects in HE such as causing potassium and magnesium loss, sodium retention, baroreceptor dysfunction, and myocardial fibrosis it also decreases the neuronal uptake... 

Pathophysiology Non-potassium-sparing diuretics are the treatment of choice to reduce fluid retention and dyspnea. Acting at specific sites of nephrons, they inhibit sodium and water reabsorption. Loop diuretics act on the loop of Henle, producing a maximal diuretic effect equivalent to 20% to 25% of the filtered sodium load and promoting the free water clearance. Currently available loop diuretics include furosemide, bumetanide, torsemide, and ethacrynic acid. Because of their potency, they are generally effective in patients with advanced renal insufficiency (glomerular filtration rates <25 ml/min) (49). 

Noble, D. and Noble, P. J. Late sodium current in the pathophysiology of cardiovascular disease consequences of sodium-calcium overload. Heart 2006, 92 ivl-iv5. Noble, D. and Varghese, A. Modeling of sodium-calcium overload arrhythmias and... 

Related to the post-traumatic microvascular damage is the pathophysiological process of vasogenic brain edema that represents a disruption of blood-brain barrier integrity, resulting in sodium and protein accumulation and osmotic fluid expansion of the brain extracellular space. Clinically, this is reflected by an increase in intracranial pressure which, if unchecked, can cause secondary compressive injury to vital brain structures. 

The sodium-channel inhibitor Amiloride is used for the treatment of chronic bronchitis, and the most frequently used anesthetic drug, lidocain, inhibits voltagegated sodium-channel a subunits, which mediate the pathophysiology of pain. 

Lamotrigine, which exerts its effects by reducing the exchange of sodium ions across the cell membrane. In addition it reduces the release of excitatory glutamate, which may be implicated in the pathophysiology of seizures. 

Four general pathophysiologic mechanisms disrupt water and electrolyte balance, leading to diarrhea. These four mechanisms are the basis of diagnosis and therapy. They are (1) a change in active ion transport by either decreased sodium absorption or increased chloride secretion (2) a change in intestinal motility (3) an increase in luminal osmolarity and (4) an increase in tissue hydrostatic pressure. These mechanisms have been related to four broad clinical diarrheal groups secretory, osmotic, exudative, and altered intestinal transit. 

Local neural irritation can occur when large doses of formulations containing sodium bisulfate as a preservative are used epidurally or intrathecaUy, probably because of the low pH and the sodium bisulfate content rather than the local anesthetic (SEDA-14, 111). Prolonged neural deficits have been described, the pathophysiology of which is controversial (SEDA-10,105). 

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