Epithelial sloughing

Asthma is a chronic inflammatory condition characterized by bronchial hyper-responsiveness and reversible airway obstruction. Cytokine release from a variety of cell types such as eosinophils, lymphocytes and other inflammatory cells produces epithelial sloughing, plasma protein extravasation from the tracheobronchial microcirculation and airway remodeling. Bronchial mucosal inflammation is present in all patients. The primary goal of asthma management is to maintain control of the disease process by reducing symptoms and improving lung function. 

Additional findings in EKC can include pseudomembrane formation (Figure 26-46) and corneal epithelial sloughing. Symblepharon, scleritis, and anterior uveitis rarely develop. Nasolacrimal system obstruction due to inflammation or adhesion of opposing surfaces, as occurs in symblepharon formation, also is a rare complication. 

Exposures to higher concentrations of vapor result in an earlier onset and greater severity of the above effects. Hoarseness rapidly progresses to aphonia. Severe tachypnea and early radiological infiltrates may appear. More severe respiratory exposures create necrotic changes in the respiratory epithelium that result in epithelial sloughing and pseudomembrane formation. There may be substantial airway occlusion from the inflammatory debris or from pseudomembranes, which can obstruct the upper airways as they form or can break off and obstruct lower airways (Vedder, 1925 Buscher and Conway, 1944 Willems, 1989). 

Rat 2, 10 min 1,500 Lung edema with bronchial epithelial sloughing and airway wall leucocyte infiltration some epithelial regeneration after 72 h Demnati et al. (1995)... 

Smooth-musele hypertrophy Mueosal edema Hyperseeretion or plugging Epithelial sloughing Normal or impaired clearanee Mural thickening Loss of cilia Impaired clearance Normal clearance... 

Keratinization, the sloughing of epithelial cells in the hair follicle, is also a natural process. In acne, however, hyperkem-tinization occurs and causes increased adhesiveness of the sloughed cells. Accumulation of these cells clogs the hair follicle, blocks the flow of sebum, and forms an acne lesion called an open comedo or blackhead. ... 

The exudative inflammatory process and sloughing of epithelial cells into the airway lumen impair mucociliary transport. The bronchial glands are increased in size, and the goblet cells are increased in size and number. Expectorated mucus from patients with asthma tends to have high viscosity. 

Dastgheib KA, Clinch TE, Manche EE, Hersh P, Ramsey J. Sloughing of corneal epithelium and wound healing complications associated with laser in situ keratomileusis in patients with epithelial basement membrane dystrophy. Am J Ophthalmol 130 297-303 (2000). 

About 1 g of cholesterol is ingested by adults each day in developed countries. A similar amount enters the lumen via the bile, synthesised from acetyl-CoA in the liver, is also released from sloughed epithelial cells. Absorption of cholesterol also occurs from the mixed micelles. Within the enterocyte, it is esterified and the cholesterol ester is incorporated into the chylomicrons. 

About 90 g of protein is ingested each day by an adult on a typical Western diet and a similar amount enters the intestine from the secretion of enzymes, proteins and from sloughed epithelial cells (Chapter 8). The proteins are hydrolysed by proteolytic enzymes. 

Mammalian skin must be tough, water-resistant, self-renewing, and rapidly healing. The outer layers of cells or epidermis consist principally of keratinocytes, epithelial cells specialized for formation of keratin (Fig. 7-31). In the inner layer of the epidermis the basal stem cells divide, providing a constant outward flow of cells which become progressively flattened, dehydrated, and filled with keratin fibrils.3 The outer layers contain only dead cells which are finally sloughed or abraded from the surface. Human epidermis is completely renewed in about 28 days ... 

Nasal mucus. The nasal mucus protects the body against airborne substances. Nasal mucus consists of mucopolysaccharides complexed with sialic acid, sloughed epithelial cells, bacteria, water (95 percent), glycoproteins and lipids (0.5 to 5 percent), mineral salts (0.5 to 1 percent), and free proteins (albumin, immunoglobulins, lysozyme, interferon, lactoferin, etc., 1 percent).13 45 111 112 The surface pH of the nasal mucosa is 5.5 to 6.5.113... 

Figure 1.1 shows the major sites of enzyme activity in the GI tract, and we will consider each of these in turn. While most of the enzymes that hydrolyse macromolecules enter the gut in the pancreatic fluid and hence are found in the lumen of the gut, there is significant peptidase activity located on the membranes of the intestinal cells, the so-called brush border. Consideration should also be given to the enzymes that are located inside the cells of the intestinal mucosa, namely, the epithelial cells or enterocytes. This is for two reasons first, the intestinal mucosa has a turnover of 3-6 days in humans and this means that the enterocytes are constantly being sloughed-off into the lumen of the gut. Thus intracellular enzymes and brush border enzymes will be found in the lumen of the gut, though the precise quantity is difficult to assess (see later in Section 1.6). 

The lumen of the intestine, especially that of the jejunum, contains the highest concentration and diversity of enzymes that are a threat to macromolecular drugs and macromolecular pharmaceutical formulations. The main sources of these enzymes will be in the pancreatic juice and the sloughed-off epithelial cells. 

The lysosomal enzymes The lysosomes are membrane vesicles ubiquitous to mammalian cells and contain a panoply of hydrolytic enzymes, estimated to be over 60 in number, that function to digest practically any biological macromolecule. They are important to the discussion of oral macromolecular drug delivery for two reasons. First, any macromolecules that escape digestion by the pancreatic and brush border enzymes are likely to be taken up into the epithelial cells by the process of endocytosis. In this process, the apical membrane invaginates and the target molecules enter endocytic vesicles that then fuse with the lysosomes and are subjected to intracellular hydrolysis by the lysosomal enzymes. Second, the sloughing-off of the epithelial cells means that the lysosomal enzymes will be released into the lumen of the intestine. They may be... 

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