Villi crypt

Altmann, G.G. Snow, A.D. (1984) Effects of 1,2-dimethylhydrazine on the number of epithelial cells present in the villi, crypts, and mitotic pool among the rat small intestine. Cancer Res., 44, 5522-5531... 

The surface of the mucosa is relatively smooth as there are no intestinal villi. Crypts of Lieberktlhn are present. Goblet cells account for more of the epithehal cells than in the small intestine. The mammalian large intestine is important for the maintenance of water and electrolyte balance. Its primary function is the reabsorption of water, sodium, chloride and volatile fatty acids it secretes potassium and bicarbonate. 

Patients with coeliac disease show the symptoms associated with malabsorption, often characterized by steatorrhoea (pale stools that float because of their high fat content) (22a). Malabsorption may have any number of causes, one of which is coeliac disease, a gluten-sensitive enteropathy. This disorder results in loss of villi, crypt hyperplasia and chronic inflammation of the small bowel mucosa. The immature cells of the small intestine are unable to absorb nutrients or to produce G1 hormones. This reduces pancreatic and bile secretion, which impedes fat absorption in the gut. Anaemia is caused by the folate and B12 deficiency due to impaired absorption (22b). Treatment of coeliac disease is by a gluten-free diet, steroids (to treat inflammation) and immunosuppressants (22c). People with unrecognized and untreated coeliac disease may have an increased risk of small bowel carcinoma. 

Immune expulsion of T. spiralis is clearly Th2- and, specifically, IL-4-dependent. However, contrary to expectations, enteropathy (as assessed by changes in villus/crypt ratios) is regulated by IL-4 and not IFN-y (Lawrence et al., 1998). Moreover, the usual severe pathology is not induced in p55 TNF receptor (TNF-R1) gene-deficient mice, which nevertheless expelled... 

Fihn, B. M., A. Sjoqvist, and M. Jodal. Permeability of the rat small intestinal epithelium along the villus-crypt axis effects of glucose transport, Gastroenterology 2000, 119, 1029-1036... 

Fig. 5. Rate of cholesterol synthesis in the mucosa along the villus-crypt axis in the rat intestine. Enriched mucosal cell fractions were obtained from the mucosa by EDTA treatment and these viable cells were subsequently incubated in the presence of [ HJwater. Panels A and B represent the rate of cholesterol synthesis expressed as the nmoles of acetyl-CoA units incorporated into cholesterol/h/mg of cell protein in the jejunum and ileum, respectively. Panels C and D represent the total activity found in the isolated cell fractions talcing into account the cell protein recovered in each fraction. The columns and bars represent means + 1 S.E.M.

Fig. 8. Rate of LDL-cholesterol uptake in the mucosa along the villus-crypt axis in the rat intestine. The rates of LDL-cholesterol uptake were determined by measuring the tissue clearance of [ C]sucrose-labeled LDL in vivo and then isolating different cell fractions from the mucosa. These clearance values were multiplied by the LDL-cholesterol concentration in plasma and expressed as the nmoles of LDL-cholesterol taken up per h/mg of cell protein (panels A and B) or as the percentage of total mucosal uptake found in each cell fraction (panels C and D). The columns and bars represent means +1 S.E.M.

The relative importance of each of these contributions to pool C is likely to be different in epithelial cells located at different points along the villus-crypt axis. The fact that cholesterol derived from synthesis and from the uptake of LDL is critically important for membrane formation and differentiation is suggested by the finding that 70-80% of total mucosal sterol synthetic activity and LDL transport activity are localized to the immature cells of the lower villus and crypt regions in both the proximal and distal intestine. In the mature absorptive cells of the upper villus in the jejunum, where most sterol absorption takes place, the rate of cholesterol synthesis appears to be suppressed. In the absence of fat absorption, cholesterol newly synthesized in these cells apparently is sloughed into the lumen and not reabsorbed. However, with active triglyceride absorption cholesterol synthesis in these cells is increased and a portion of this sterol appears in the intestinal lymph. Only under this condition does pool B apparently supply sterol for lipoprotein formation. 

The main absorbed product of phospholipid digestion is monoacyl-phosphatidylcholine (lysophosphatidylcholine). A fatty acid is re-esterified to position 1 to form phosphatidylcholine by an acyl transferase located in the villus tips of the intestinal brush border. The function of this phospholipid will be to stabilize the triacylglycerol-rich particles, or chylomicrons, exported from the cell as described later. It is thought that the phosphatidylcholine used for the synthesis and repair of membranes in the enterocytes (cells with a rapid turnover) is synthesized by the classical CDP-choline pathway (section 7.1) in cells at the villus crypts. 

Figure 3 Schematic of crypt-villus cellular axis and components of villus central lac-teal. (From Ref. 77.)...

Figure 14 Ion transport pathways responsible for water flux across intestinal epithelia. Sodium absorption in villus tip cells (left) stimulates water absorption, while chloride channel exit in crypt cells (right) stimulates water secretion.

In those infections that are associated with enteropathy (exemplified by T. spiralis), no experimental manipulation has, until recently, been able to separate enteropathy and immune expulsion - if one is abrogated, so is the other. This chapter illustrates how the two processes can be separated, and discusses implications of this for understanding immune expulsion of gut nematodes and the prospects for anti-nematode vaccines that cause no ill effects at either the initial induction of immunity or the expression of protective responses. The definition of that which consitututes enteropathy may vary between authors, but we take as our primary definition the most destructive and quantifiable changes in intestinal tissue that are associated with expulsion, villus atrophy and crypt hyperplasia. 

The morbidity and mortality that are often associated with human GI helminth infections reflect in part the nutritional consequences of diarrhoea and malabsorption, and the resulting malnutrition that can accentuate the effects of infection by suppressing the protective immune response as well as compromising intestinal repair (Ferguson et al., 1980 Keymer and Tarlton, 1991 Cooper et al, 1992). In experimental rodents the pathology associated with infection is characterized by villus atrophy, crypt hyperplasia, goblet cell hyperplasia and infiltration of the mucosa by a variety of... 

T. spiralis-infected control, showing crypt hyperplasia and villus atrophy (C) day 13 p.i. T. spiralis-infected TNF-R1, mice, showing normal appearance, similar to (A) (D) day 13 p.i. T. sp/ra//s-infected IL-4, mice, again showing a normal appearance. Bar represents 100 pm. Reproduced from Lawrence etal. (1998), with permission. 

Fig. 18.3. Burdens of adult T. spiralis and development of intestinal pathology in mast-cell-deficient N/W mice. W/W mice and their normal littermates were infected with 400 T. spiralis muscle larvae. (A) Adult worm burdens are represented as mean + sem, five mice per group (, significantly different from day 6 p.i., P< 0.05). (B) Crypt and villus lengths were measured at day 0 and day 13 p.i. Results are expressed as mean + sem for five mice per group (, significantly different from uninfected animals (day 0), P< 0.05). Unpublished data.

Figure 8.2 Rat duodenal cells divide in the crypts of Lieberktihn and differentiate while migrating to the villus tips within approximately 48 h. The crypt cells take up iron from the blood, and are thereby able to sense the body s state of iron repletion. They migrate to the villus tips where this information determines their iron absorption capacity from the intestinal lumen. Adapted from Schumann et al., 1999, by permission of Blackwell Science.

The situation prevailing in the crypt cell at the beginning of its differentiation into an enterocyte and before it has begun to climb towards the villus is shown in the lower panel. The cell s iron requirements are supplied by receptor-mediated diferric transferrin uptake from the basolateral membrane. The TfR in turn is involved in an interaction with the HFE protein, which decreases the affinity of TfR for diferric transferrin. The level of transferrin saturation, or some other factor, determines the amount of iron taken up, and presets the IRP system at a level that corresponds to the iron requirements of the organism. 

More detailed knowledge of the mechanisms of iron absorption from the gastrointestinal tract of mammals has advanced by leaps and bounds in the last few years, with the cloning of key participants at both the apical and basolateral faces of the mucosal endothelial cells. The extraordinarily far-sighted contribution of William Crosby and Marcel Conrad, nearly 40 years ago (Conrad and Crosby, 1963 Crosby, 1963), reminded us of the key role of body iron status in determining the level at which iron absorption will be set within the cells of the crypts of Lieberkiihn when they differentiate and move up to the villus tips to play their key role in... 

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