Pathogenesis of infectious diarrhea: GUT PHYSIOLOGY Part 1

GUT PHYSIOLOGY Part 1One of the main functions of the gut is the selective active inward transport of ions and nutrient solutes that is followed by the passive movement of water. Highly simplified schematic representations of a small intestinal villus and of fluid uptake and physiological secretion are shown in Figures 1 and 2. The driving force is sodium/potassium ATPase situated in the basolateral membrane of enterocytes, which maintains a low intracellular sodium concentration and a high regional sodium concentration in the intercellular spaces, thus creating the electrochemical gradient favourable for sodium ion entry; chloride ions follow sodium ions. ventolin inhalers
Sodium/potassium ATPase also drives secretion in crypt cells. The key difference is the location of the carrier systems responsible for the facilitated entry of the actively transported species. In villus cells, the carriers are present in brush borders, whereas in crypt cells they are located in basal membranes. This is responsible for the vectorial aspects of ion/fluid traffic in villus/crypt assemblies. However, it is clear that several factors in addition to ente-rocytes are involved in regulating fluid transport in the gut, including the enteric nervous system (ENS) and the anatomy of the microcirculation. The latter plays a profoundly important role in the uptake of fluid. At the tips of villi, osmolalities ranging from 700 to 800 mOsm/kg H2O have been demonstrated in the human gut, which generates huge osmotic forces. Thus, current perceptions are that enterocytes are responsible for generating this gradient (Figure 2) and that the blood supply acts as a countercurrent multiplier, which amplifies the gradient in a manner analogous to the loops of Henle in the kidney. The hypertonic zone has been demonstrated directly in whole villi of infant mice by the changing morphology of erythrocytes (Figure 3); in the lower regions of villi, they show characteristic discoid morphology, whereas in the upper region they are crenated, indicating a hyperosmotic environment. The hypertonicity is dissipated if the blood flow is too slow and washed out if too fast. It is the villus unit rather than enterocytes by themselves that is responsible for fluid uptake. Another consequence of the microcirculatory anatomy is that the villus tip regions are relatively hypoxic.

Simplified schema

Figure 1) Simplified schema: integrated structure and function of the small intestinal villus. Note the central arterial vessel (AV), which arborizes at the tip into a capillary bed drained by a subepithelial venous return (VR). Movement of sodium into the VR creates a concentration gradient between VR and AV, causing absorption of water from AV and surrounding tissue. This results in a progressive increase in the osmolarity of incoming blood moving into the tip region through to the VR. Tip osmolarity is about three times higher than normal. Hyper-osmolarity has been demonstrated in humans and can be inferred in mice from the morphology of erythrocytes, which changes during ascent of the same vessel from the base to the tip regions of the villi (see Figure 3). The shaded areas indicate a vertical increase in osmolarity. The left crypt represents normal physiological secretion; the right crypt represents hypersecretion. ENS Enteric nervous system (depicted schematically and not anatomically). Reproduced with permission from reference 98

Simplified schematic representation

Figure 2) Simplified schematic representation of electrolyte transport by ileal mucosal tissue and its consequence for absorption (a) and secretion (b). Active processes involve the movement of ions and nutrient solutes; water follows passively. a) Two methods of sodium ion cotransport are shown involving a glucose-linked symport and two coupled antiports; one of the latter results in the cotransport of chloride ions. The coupled antiports are functionally linked via hydrogen and bicarbonate ions, the relative concentrations of which are a reflection of metabolic activity. These processes occur within the same cells but are shown separately for clarity. The driving force for sodium ion uptake is the low sodium ion concentration maintained by the sodium/potassium pump (ATPase) in the basolateral membrane, which creates the electrochemical gradient that promotes the inward movement of sodium ions; chloride ions follow sodium ions by diffusion. Water is drawn osmotically across the epithelium paracellularly (ie, across tight junctions) and/or transcellularly, the former pathway accounting for approximately 80% of fluid movement. b) Secretion is the result of the coupled entry of sodium and chloride ions across the basolateral membrane. Sodium ions are recycled by the sodium/potassium pump and chloride ions exit by diffusing down an electrochemical gradient and across the undifferentiated crypt cell apical membrane; sodium ions follow chloride ions, and water follows passively. Note: The driving force results from the same mechanism that powers absorption, ie, the sodium/potassium pump located in the basolateral membrane; it is the location of the ‘port’ ‘diffusion’ systems that determines the vectorial aspects of ion movement. The tight junctions are less tight in the crypts than in the villi. The apical membrane of the crypt cell is undifferentiated and only acquires microvilli during ascent into villous regions. • Na+/K+ pump; • Symport, antiport or diffusion channel

Villus circulation in neonatal mice.

Figure 3) Villus circulation in neonatal mice. Whole collapsed villi isolated, fixed and stained as in references 2 and 3. a) Lower intestine of a normal eight-day-old mouse. Note the crenated cells (asterisks) in the apical region of the villus and the discoid red cells (arrows) in the basal region; scale bar = 60 цm. Reproduced with permission from reference 2. b) Villi of neonatal mouse, 48 h after infection with mouse rotavirus, are short, shrivelled and markedly ischemic; scale bar = 150 цт). c) Villi of neonatal mouse, 96 h after infection with mouse rotavirus. Vascular beds are distended and engorged with red blood cells (hyperemic); scale bar = 150 цт. Reproduced with permission from reference 2. Reproduced with permission from reference 3

This entry was posted in Diarrhea and tagged Bibrio cholerae, Clostridium difficile, Diarrhea, Escherichia coli, Shigella dysenteriae.