The structure and function of the intestine in conditions affecting salt and water homeostasis

Munday, Enid Mary Duckworth (1983) The structure and function of the intestine in conditions affecting salt and water homeostasis. University of Southampton, Doctoral Thesis.

Abstract

In this study, the physiological significance of the actions of aldosterone and angiotensin in regulating salt and water absorption across intestinal epithelia in relation to their major role in salt and water homeostasis has been investigated. Various methods were used to manipulate endogenous levels of the hormones, and transport capacity of the rat jejunum under these conditions was measured. Experimental reduction of extracellular fluid volume increases jejunal fluid transport and, conversely, expansion of the extracellular fluid by salt loading depresses jejunal transport. This suggests that aldosterone may be important in the intestine's contribution to regulation of extracellular fluid volume. However, when aldosterone levels were greatly reduced by adrenalectomy, and extracellular fluid volume maintained with sodium chloride, fluid transport was unchanged from normal values, suggesting the importance of another factor in regulating intestinal absorption under conditions of changing extracellulax fluid volume. The possibility of this being the renin-angiotensin system was investigated. Reduction of extracellular fluid in adrenalectomised rats (i.e. in the absence of aldosterone) caused a significant increase in jejunal fluid absorption. This effect was attenuated by the removal of the kidneys (i.e. reduction in circulating angiotensin). This supports the suggestion that the response of the intestine to changing extracellular fluid is mediated by the renin-angiotensin system. Under the conditions used, there were measureable changes in the reninangiotensin system, for example, the estimated half-life of circulating angiotensin in adrenalectomised rats with reduced extracellular fluid was significantly lower than that in both normal rats and adrenalectomised rats with maintained extracellular fluid volume.The experimental procedures used also had very significant effects on the cardiovascular system. Thus during salt depletion following adrenalectomy, blood pressure was 50% of normal values and there were significant reductions in blood and plasma volumes and haematocrit. Cardiac output, heart rate and stroke volume were also significantly lower than control values. Changes in morphology were also monitored. After adrenalectomy, with maintained extracellular fluid volume, there was a reduction in crypt cell proliferation which was reflected in reduced crypt-villus length, but with unchanged life expectancy. These effects were unchanged after long-term adrenalectomy. Observations on the effects of adrenalectomy were supported by studies on in vitro uptake of (3H)-thymidine. Salt loading had no effect on cell proliferation or crypt-villus length, suggesting that aldosterone plays no part in the control of these parameters and the effect of adrenalectomy is attributable to loss of hormones other than aldosterone. Adreralectomy with reduced extracellular fluid volume caused a much greater reduction from normal values than adrenalectomyy with maintained extracellular fluid, an effect probably partly attributable to nutritional and cardiovascular factors. Changes in cell proliferation and crypt-villus length did not, in any experimental condition, correspond to changes in fluid absorption. It appears that, within the limits of changes imposed in this investigation, the response of the jejunal mucosa to hormonal mediation of salt and water tranfer is unrelated to changes in cell kinetics and crypt-villus size.

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