Intracellular electrolytes

Patients with tumor lysis syndrome experience a wide range of metabolic abnormalities. The massive cell lysis that occurs leads to the release of intracellular electrolytes, resulting in hyperkalemia and hyperphosphatemia. High concentrations of phosphate bind to calcium, leading to hypocalcemia and calcium phosphate precipitation in the renal tubule. Purine nucleic acids are also released that are subsequently metabolized to uric acid... 

The methods of solute transfer across the serosal/basolateral membrane can include ion channels and antiporters similar to those described earlier. In the case of serosally located cation channels, these primarily work because the intracellular electrolyte concentration is high enough to overcome the electrical gradient (e.g. some K+ channels). For anion channels, the negative charge inside the cell compared with the blood will help drive (repel) anions from the cell (e.g. CL efflux on voltage-sensitive channels in the intestine [58]). In the case of antiporters, the operation is fundamentally the same as that used in the mucosal membrane, except that the driving force is derived from an ion... 

Wehling M. Effects of aldosterone and mineralocorti-coid receptor blockade on intracellular electrolytes. Heart Fail Rev. 2 005 10 39-46. 

Intracellular electrolytes are potassium, magnesium, and some calcium. 

Rhabdomyolysis—The breakdown of muscle tissue and release of myoglobin and intracellular electrolytes into the circulation due to a variety of causes such as crush injuries, drug-induced immobilization, and status epilepticus. It often leads to acute renal failure. 

Take a look again at Figure 10.2. At LF, the membrane impedances are high and AC current through the membranes is very small the tissue behaves as a frequency-independent AC conductor without contribution from the cell membranes and intracellular electrolytes. At HF, the membranes have low impedance and the current contribution of the intracellular electrolytes is high. The tissue also then behaves as an AC conductor but with a higher conductance than at LF. 

Effect on Electrolytes. The administration of human growth hormone raises the intracellular levels of electrolytes, leads to a loss of bone calcium, and reduces urinary levels of phosphorus, potassium, and sodium. The increase in intracellular electrolytes may result from an increase in the cellular mass. Mobilization of bone calcium leads to osteoporosis in acromegaly and calciuria. Two explanations offered for this are (1) increased glomerular filtration combined with inhibition of tubular reabsorption, and (2) stimulation of parathyroid secretion. 

Potassium (K" ) is the major intracellular electrolyte and its concentration in the body is regulated by the kidney although corrections of disturbances in potassium balance require several hours (Giebisch 1998). Whereas a marked decrease is required (20-40 %) to induce reabsorption in the kidney, an increase results in a prompt rise in clearance. The reabsorption of most occurs in the proximal tubule by passive transport, while secretion (active and passive) occurs in the distal tubule and collecting ducts. However, depending on body needs, secretion can be replaced by reabsorption. 

Identify the electrolytes primarily found in the extracellular and intracellular fluid compartments. 

The intracellular fluid (ICF) represents the water contained within cells and is rich in electrolytes such as potassium, magnesium, phosphates, and proteins. O The ICF is approximately two-thirds of TBW regardless of gender. For a 70-kg man, this would mean that the TBW is 42 L and the ICF is approximately 28 L. For a 70-kg woman, these values would be 35 L and 24 L, respectively. Note that ICF represents approximately 40% of total body weight in men and approximately 33% of total body weight in women. 

One model of an ionic mechanism of action of Li+ in affective disorders has been proposed, in which the receptors for Li+ are ion channels and cation coenzyme receptor sites, and in which the presence of intracellular Li+ in excitable cells results in the displacement of exogenous Na+ and/or other intracellular cations [13]. It has been suggested that this could lead to a decrease in the release of neurotransmitters alternatively it may be that this intracellular Li+ is altering a preexisting, disease-related electrolyte imbalance [14]. A number of observations of such imbalances in affective disorders have been made depression is associated with elevated levels of intracellular Na+ [15] retention of Li+ is observed in manic-depressive patients prior to an episode of mania [ 16] and Na+/K+ activity is defective during both mania and depression [17]. 

The transport behavior of Li+ across membranes has been the focus of numerous studies, the bulk of which have concentrated upon the human erythrocyte for which the Li+ transport pathways have been elucidated and are summarized below. The movement of Li+ across cell membranes is mediated by transport systems which normally transport other ions, therefore the normal intracellular and subcellular electrolyte balance is likely to be disturbed by this extra cation. Additionally, Li+ has been shown to increase membrane phospholipid unsaturation in rat brain, leading to enhanced fluidity in the membrane, which could have repercussions for membrane-associated proteins and for membrane transport properties. 

Additionally, tegaserod at low nanomolar concentrations increases intracellular cAMP concentrations in crypt cells isolated from rat distal colon and stimulates chloride and water secretion by activation of 5-HT4 receptors [34,35], These findings suggest a modulatory effect on intestinal electrolyte and water secretion in vivo. 

All eukaryote cells are faced with differences in intracellular solute composition when compared with the external environment. Many eukaryotes live in seawater, and have cells which are either bathed in seawater directly, or have an extracellular body fluid which is broadly similar to seawater [3]. Osmoregulation and body fluid composition in animals has been extensively reviewed (e.g. [3,15-21]), and reveals that many marine invertebrates have body fluids that are iso-osmotic with seawater, but may regulate some electrolytes (e.g. SO2-) at lower levels than seawater. Most vertebrates have a body fluid osmotic pressure (about 320mOsmkg 1), which is about one-third of that in seawater (lOOOmOsmkg ), and also regulate some electrolytes in body fluids at... 

Figure 1. Solute transfer across an idealised eukaryote epithelium. The solute must move from the bulk solution (e.g. the external environment, or a body fluid) into an unstirred layer comprising water/mucus secretions, prior to binding to membrane-spanning carrier proteins (and the glycocalyx) which enable solute import. Solutes may then move across the cell by diffusion, or via specific cytosolic carriers, prior to export from the cell. Thus the overall process involves 1. Adsorption 2. Import 3. Solute transfer 4. Export. Some electrolytes may move between the cells (paracellular) by diffusion. The driving force for transport is often an energy-requiring pump (primary transport) located on the basolateral or serosal membrane (blood side), such as an ATPase. Outward electrochemical gradients for other solutes (X+) may drive import of the required solute (M+, metal ion) at the mucosal membrane by an antiporter (AP). Alternatively, the movement of X+ down its electrochemical gradient could enable M+ transport in the same direction across the membrane on a symporter (SP). A, diffusive anion such as chloride. Kl-6 refers to the equilibrium constants for each step in the metal transfer process, Kn indicates that there may be more than one intracellular compartment involved in storage. See the text for details...

The intracellular environment of eukaryote cells can be subdivided into many regions, including the organelles, nucleus, cytoplasm and the cell periphery. Thus solutes must be delivered to the right intracellular compartment at the correct time to efficiently serve cellular biochemistry. Uncharged solutes such as glucose presumably diffuse across the cell, and the traditional view held until recently was that the major electrolytes, such as Na+,K+,CF and Mg2+, also move around the cell by simple diffusion to eventually arrive at the relevant subcellular compartment by chance. 

Volumes of the intracellular and extracellular body fluid compartments are kept constant by the osmotic pressure, which is created by the concentration of dissolved ions (electrolytes) in each compartment. The normal osmotic concentration is in the range of 280-310 mOsm/L. 

Laboratory assessment of the composition of the blood plasma is often carried out in clinical chemistry. Among the electrolytes, there is a relatively high concentration of Na"", Ca and Cl ions in the blood in comparison with the cytoplasm. By contrast, the concentrations of IC, Mg "", and phosphate ions are higher in the cells. Proteins also have a higher intracellular concentration. The electrolyte composition of blood plasma is similar to that of seawater, due to the evolution of early forms of life in the sea. The solution known as physiological saline" (NaCl at a concentration of 0.15 mol L ) is almost isotonic with blood plasma. 

Management has three important caveats. Firstly, it is mandatory that the causative lesion be reliably identified and, if possible, corrected. Here it should be remembered that a suboptimal intake of this vitamin is frequently seen in those who have diets deficient in vegetables and particularly fresh leafy products found in salads. Secondly, once treatment is initiated, there may be precipitous falls in serum potassium as ineffective haematopoiesis suddenly corrects and so removes the substantial delivery of the intracellular cation to the circulation renal compensation requires slightly longer to adapt and in that interval cardiac arrhythmia and death can occur. Eor this reason patients either need to have plasma electrolytes monitored initially or arbitrary oral potassium replacement supplied. Thirdly, there may be a transient increase in haemoglobin, which then reaches a plateau, and this is the consequence of exhausting available iron stores so that monitoring is necessary or supplementation with simple ferrous salts provided. 

The concentrations and distribution of electrolytes are not fixed, because cell membranes are permeant to ions and to water. Movement of ions and water in and out of cells is determined by the balance of thermodynamic forces, which are normally close to equilibrium. Selective changes of ion concentrations cause movement of water in or out of cells to compensate for these alterations. The kidneys are a major site where changes in salt or water are sensed. The loss of fluids due to illness or disease may alter intracellular and extracellular electrolyte concentrations, with attendant changes in fluid movement in or out of cells. Changes of extracellular or intracellular ion concentrations, particularly for potassium, sodium, and calcium, can have profound effects on neuronal excitability and contractility of the heart and other muscles. 

E. Murphy, Measurement of intracellular ionized magnesium, Miner. Electrolyte Metab. 19 (1993) 250-258. 

Mechanism of Action An electrolyte that is necessary for multiple cellular metabolic processes. Primary action is intracellular. Therapeutic Effect Needed for nerve impulse conduction and contraction of cardiac, skeletal, and smooth muscle maintains normal renal function and acid-base balance. 

---