Interstitium

Neurotransmitter transporters determine the neurotransmitter concentration in the interstitium. High-affinity transporters can efficiently remove neurotransmitter from the extracellular space because cellular uptake is typically coupled to the translocation of sodium ions. 

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

In the interstitium, angiotensin II induces proliferation of mesangial cells and fibroblasts and the synthesis of collagen and other matrix molecules by these cells via the ATI receptor. Moreover, by the concomitant stimulation of chemoattractant cytokines, inflammation is induced. These processes are mediated by endothelin, transforming growth factor(3, and reactive oxygen species, and finally lead to interstitial fibrosis and glomerulosclerosis observed in hypertension and diabetes. 

The ICRP deposition model estimates the fraction of inhaled material initially retained in each compartment (see Figure 3-2). The model was developed with five compartments (1) the anterior nasal passages (ET,) (2) all other extrathoracic airways (ET2) (posterior nasal passages, the naso- and oropharynx, and the larynx) (3) the bronchi (BB) (4) the bronchioles (bb) and (5) the alveolar interstitium (AI). Particles deposited in each of the regions may be removed and redistributed either upward into the respiratory tree or to the lymphatic system and blood by different particle removal mechanisms. 

Factors known to influence the clearance of drugs from interstitial sites, following extravasation or parenteral interstitial or transepithelial administration, include size and surface characteristics of particles, formulation medium, the composition and pH of the interstitial fluid, and disease within the interstitium. Studies indicate that soluble macromolecules smaller than 30 nm can enter the lymphatic system, whereas particulate materials larger than 50 nm are retained in the interstitial sites and serve as a sustained-release depot. The use of lipids or an oil in a formulation and the presence of a negative surface charge all appear to... 

More specifically, the blood-gas interface consists of the alveolar epithelium, capillary endothelium, and interstitium. The alveolar wall is made up of a single layer of flattened type I alveolar cells. The capillaries surrounding the alveoli also consist of a single layer of cells — endothelial cells. In between the alveolar epithelium and capillary endothelium is a very small amount of interstitium. Taken together, only 0.5 pm separates the air in the alveoli from the blood in the capillaries. The extreme thinness of the blood-gas interface further facilitates gas exchange by way of diffusion. 

Acute drug-related hypersensitivity reactions (allergic responses) may cause tubulointerstitial nephritis, which will damage the tubules and interstitium. These reactions are most commonly observed with administration of methicillin and other synthetic antibiotics as well as furosemide and the thiazide diuretics. The onset of symptoms occurs in about 15 days. Symptoms include fever, eosinophilia, hematuria (blood in the urine), and proteinuria (proteins in the urine). Signs and symptoms of acute renal failure develop in about 50% of the cases. Discontinued use of the drug usually results in complete recovery however, some patients, especially the elderly, may experience permanent renal damage. 

After intratracheal instillation of nickel chloride or nickel sulphate in rats, a modest inflammatory response with increased number of macrophages and polynuclear leucocytes was obtained, together with increased activities of lactate dehydrogenase and -glucuronidase in bronchoalveolar fluid [351]. More severe lesions were characterized by type II cell hyperplasia with epithelialization of alveoli, and in some animals, fibroplasia of the pulmonary interstitium. By inhalation in rats, the nickel salts produced chronic inflammation and degeneration of the bronchiolar epithelium [352, 353]. There was also atrophy of the olfactory epithelium and hyperplasia of the bronchial and mediastinal lymph nodes. Nickel sulphate also produced a low incidence of emphysema and fibrosis [353]. 

Figure 3. A detailed depiction of a tiny section (C in Figure 1) of this tumo11 showing tumor cells, interstitium, a small blood vessel and the route that a drug i the chemotherapeutic treatment takes. Adapted from Jain.45...

Figure 4. A schematic of tumor cells (or small colonies of tumor cells) with extracellular fluid from the interstitium trapped between them. The electrochemical double layer is indicated for each negatively charged tumor cell with positive ions (in extra-cellular fluid) poised against the negative charge.25...

The potential is the potential difference between the plane of shear (or slipping plane) and the bulk solution. From Eq. (4), it is clear that for a given situation of water (electrolyte) in the interstitium, the Ueo is proportional to the zeta potential and to the applied field strength. Also in a real situation of EOD, it is necessary to use the so called length-averaged value of the zeta potential in order to take into account the effect of the axially variable zeta potential on the electroosmotic velocity. 

It should be noted from Eq. (4) that for the EOD to occur, the passage of electric current is not required, if ideally one could develop high E (V cm 1) without the passage of significant electrical current. However, in practice, the cell-interstitium medium has a given resistance R so that... 

Immunocytochemistry and in situ hybridization techniques were used to detect HIV-1 infected cells in the testis (P5), excurrent ducts, and prostate. Distinct pathologic changes were observed in the majority of testis of AIDS patients that included azoospermia, hyalinization of the boundary wall of seminiferous tubules, and lymphocytic infiltration of the interstitium. In the testis, many white blood cells were shown to the CD4 + HIV-1 positive cells of lymphocy-tic/monocytic morphology, found in the seminiferous tubules and interstitium of the testis, epididymal epithelium, and connective tissue of the epididymis and prostate. There was no evidence of active HIV-1 infection in germ cells or Sertoli cells of the seminiferous tubules or other epithelial cells lining the excurrent ducts or prostatic glands. 

The function of the loop of Henle is to enable production of a concentrated urine. It does this by generating a hypertonic interstitium, which provides a gradient for water reabsorption from the collecting duct. This, in turn, occurs under the control of antidiuretic hormone (ADH). There are several important requirements without which this mechanism would not work. These include the differential permeabilities of the two limbs to water and solutes and the presence of a blood supply that does not dissipate the concentration gradients produced. This is a simplified description to convey the principles. 

Descending limb Fluid entering is isotonic. Water moves out down a concentration gradient into the interstitium, concentrating the urine within the tubules. 

Thick ascending limb This limb is also impermeable to water. It contains ion pumps to pump electrolytes actively into the interstitium. The main pump is the Na+/2C1 /K+ co-transporter. Fluid leaving this limb is, therefore, hypotonic and passes into the distal convoluted tubule. 

Collecting duct The duct has selective permeability to water, which is controlled by ADH. In the presence of ADH, water moves into the interstitium down the concentration gradient generated by the loop of Henle. 

The pulmonary lymphatic system contributes to the clearance of fluid and protein from the lung tissue interstitium and helps to prevent fluid accumulation in the lungs [108], The lymphatic endothelium allows micron-sized particles (e.g. lipoproteins, plasma proteins, bacteria and immune cells) to pass freely into the lymph fluid [103], After administration of aerosolised ultrafine particles into rats, particles were found in the alveolar walls and in pulmonary lymph nodes [135], which suggests that drainage into the lymph may contribute to the air-to-blood transport of the inhaled particles. 

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