Importance of the Microcirculation to Intestinal Secretion
T. S. Gaginella in Regulatory Mechanisms — in — Gastrointestinal Function, 2017
Active transport of glucose and amino acids increases epithelial conductance through a specific effect of increasing tight junctional permeability.18This process requires mucosal nutrients, Na, and metabolic energy, and is mediated through activation of Na-coupled organic transport and cytoskeletal structures. This response is dependent on adequate oxygenation, and therefore ischemia may reduce mucosal permeability through tight junctions.142Dilations form within the tight junctions, and their resistance to paracellular transport decreases. This process increases the absorption of nutrients past the tight junctions through increased solvent drag. The solvent drag is driven by the active transport into, and consequent osmotic pressure in, the lateral spaces. Pressure-driven secretion across the epithelium would be increased when tight junction dilations occur, but the concurrent active absorption may mask this secretion.143
Fluid Compartments
Lara Wijayasiri, Kate McCombe, Paul Hatton, David Bogod in The Primary FRCA Structured Oral Examination Study Guide 1, 2017
Capillary wall: consists of a single layer of simple squamous epithelium and a basement membrane (basal lamina). Capillaries connect arteries and veins within organ systems across a branched network called the capillary bed. The more metabolically active an organ is, the larger the capillary bed. Small molecules (<3 nm) such as water, oxygen and carbon dioxide cross the capillary wall through the space between cells (paracellular transport), while larger molecules (>3 nm) such as albumin and other large proteins pass through transcellular transport carried inside vesicles. There are three main types of capillaries: Continuous: uninterrupted lining with tight junctions and complete basal lamina. Allow passive diffusion of lipid-soluble molecules and movement of small molecules such as water and ions through intercellular clefts. Skeletal muscle and skin have numerous transport vesicles, whereas CNS (blood–brain barrier) has few, so sealing the paracellular space.Fenestrated: endothelial cells have pores or windows (60–80 nm in diameter) and a complete basal lamina. Allow a limited amount of proteins to diffuse. They are located in intestines, pancreas, endocrine glands and renal glomeruli.Sinusoidal: large open-pore (30–40 μm in diameter) capillaries, large gaps between cell junctions and a discontinuous basal lamina. Allow red and white blood cells (7.5–25 μm diameter) and serum proteins to pass. Present in bone marrow, lymph nodes, liver, spleen and adrenal glands.
Immune function of epithelial cells
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
The other pathway for movement across epithelial barriers is to go around the cell, through the intercellular junctions that join adjacent cells together. This is termed the “paracellular pathway.” Movement of solutes and water through the paracellular pathway can only be passive. There is no way to harness cell energy directly to this process, and paracellular transport is completely dependent on concentration gradients across the barrier epithelium, or indirectly harnessed to osmotic or electrical gradients established by other activities of the epithelial cell.
Formulation of acyclovir-loaded solid lipid nanoparticles: 2. Brain targeting and pharmacokinetic study
Published in Pharmaceutical Development and Technology, 2019
Sanaa A. El-Gizawy, Gamal M. El-Maghraby, Asmaa A. Hedaya
The blood-brain barrier (BBB) is the major obstacle for the delivery of many drugs to the brain. The physicochemical and structural characters of the drugs, such as the molecular weight, hydrogen bonding, and the lipophilicity are the major parameters that affecting the passage of the drugs across the BBB (Qin et al. 2010; Matsumoto et al. 2016). There are several mechanisms for drug transport across the BBB. Paracellular transport is for hydrophilic substances. Transcellular passive diffusion is a mechanism for low molecular weight lipophilic drugs transport (van Rooy et al. 2011; Matsumoto et al. 2016). Most drugs enter the brain in their free form via the transcellular pathway. However, SLNs are larger and enter the brain via endocytosis. Endocytosis at the BBB is either receptor binding or adsorptive-mediated endocytosis (AME). It was observed an enhanced brain uptake due to the effect of tween 80 in LDL-mediated endocytosis and P-gp inhibition at the BBB (Prabhakar et al. 2013). AME is originated by the binding of cationic elements (such as nanoparticles coated with chitosan) to negative charges on the BBB membrane (Lu 2012). Another mechanism for the transport of drugs through the BBB is the carrier-mediated transcytosis. Only drugs that have similar characters of the endogenous carrier ligands will be transported (van Rooy et al. 2011).
Cell-cell junctions: structure and regulation in physiology and pathology
Published in Tissue Barriers, 2021
Mir S. Adil, S. Priya Narayanan, Payaningal R. Somanath
Two mechanisms have been proposed for the paracellular transport of solutes or ions at TJs. Whereas these molecules pass through a paracellular channel formed by the TJ strands in the ‘pore’ pathway, they supposedly pass through breaks in the TJ strands in the ‘leak’ pathway. The pore pathway can be sensed by the diffusion potential when it is selectively permeable to charged ions. The pore pathway is also permeable to uncharged solutes such as small polyethylene glycols, in a size-selective manner. On the contrary, the leak pathway is permeable to small and larger solutes with >8 Å diameter which includes both ions and uncharged solutes, and is not very size-selective, although there is a size limit for permeation. This mechanism presumably relies on the breaking and reorganization of the TJ strands.72
Gingival epithelial barrier: regulation by beneficial and harmful microbes
Published in Tissue Barriers, 2019
Naoki Takahashi, Benso Sulijaya, Miki Yamada-Hara, Takahiro Tsuzuno, Koichi Tabeta, Kazuhisa Yamazaki
A primarily structural bond between epithelial cells is created by junctional molecules, including tight junctions, adherens junctions, and gap junctions8,26 (Figure 1). Tight junctions are responsible for paracellular transport of ions, water, and solutes due to their semipermeable structure.28 Several proteins are found in the tight junctions, such as occludin,29 claudins,30 and zonula occludens (ZO) protein ZO-1, ZO-2, and ZO-3.30–32 Occludin has been detected in the gingival epithelium’s surface layer, whereas claudin-1 was found in the uppermost layer.26 Claudins have barrier properties, which directly regulate gate function at paracellular tight junction channels.30 Adherens junctions play a vital role in controlling the junctional complex activity.8 Adherens junctions are cell-to-cell adhesion sites where the actin-based cytoskeleton and cytoplasmic components are constructed, also known as the classic cadherins function.33 The intercellular communication in gap junctions is involved in homeostasis, regeneration, and developmental processes.34 Furthermore, gap junctions regulate the reciprocal exchange of metabolites and ions of molecular weight ≤1 kDa, such as cyclic adenosine monophosphate and Ca,35+ between adjacent cells. The form of this junction is a head-to-head docking of hexameric structures called connexons, and membrane proteins called connexins.36
Related Knowledge Centers
- Epithelium
- Gastrointestinal Tract
- Glucose Transporter
- Osmosis
- Transcellular Transport
- Cell Membrane
- Levothyroxine
- Renal Physiology
- Solvent Drag
- Sodium/Glucose Cotransporter 1