O. J. J. Cluysenaer

Methods and Procedures

Albumin concentration in serum was determined electrophoretically with cellulose acetate as vehicle (483). Since this method involves the use of amido-black which binds more strongly to albumin than to the globulin fractions, the values given are relatively high. Controls (n = 32): 45.8–55.1 g/1.

Causes of hypoalbuminemia

Quantitative changes in serum albumin concentration represent an important indicator of the presence of disease or its progression or improvement. The significance of serum albumin estimations is limited to varying degrees of hypoalbuminemia, since, with the exception of cases of acute dehydration, hyperalbuminemia does not occur.

Association with Other Diseases

Reports on the association of coeliac sprue with other diseases have regularly been published (56, 764). The fact that some coeliacs suffer from concomitant diseases is as such not strange. The incidence of some conditions, however, exceeds that in the remainder of the population. A well-known example of this is the association of coeliac sprue with dermatitis herpetiformis (DH) (57, 106, 287, 296, 557, 560, 849). The association between coeliac sprue and other diseases is much less pronounced, but the possibility of a certain relation between these diseases and coeliac sprue is still open for the time being.

Pathogenesis of Coeliac Sprue

Although the coeliac sprue syndrome was accurately described almost 100 years ago (305), little is known with certainty about its aetiology and pathogenesis at the present time. On the other hand it cannot be denied that particularly in the past 25 years — unmistakable advances have been made in this respect. An important event in this context was the discovery that the presence in the diet of a protein fraction from certain cereals caused the symptoms of coeliac sprue (208, 209). On the other hand, the detection of villous abnormalities and inflammatory changes in the mucosa of the small intestine (663) and the introduction of a simple and elegant method of obtaining biopsy specimens from the intestinal mucosa (185, 779) facilitated as well as stimulated research into the nature of this disease and its pathogenesis. Another important advance was made with the recent introduction of facilities for culturing mucosal biopsies, on the basis of which research into the pathogenesis of the disease is possible in vitro (109, 446, 859).

Intestinal Digestion and Absorption

The interaction between the contents of the lumen and the mucosa of the small intestine takes place at and via the membrane which separates one from the other. Their interface is greatly enlarged by the presence of mucosal folds (valvulae conniventes of Kerckring), intestinal villi, and microvilli. This surface enlargement is quite pronounced, particularly in the proximal segment of the small intestine (921). The total area of the interface between the enterocytes and the intestinal lumen has been estimated to equal that of a lawn-tennis court (180, 808). It is not quite clear why this surface area should be so large. An obvious suggestion would seem to be that it is required for optimal absorption. However, experience gained with patients after resection of a large portion of the small intestine contradicts this. The available surface area is evidently substantially larger than would be strictly necessary; there is, it seems, a considerable functional reserve. This is also apparent from the large amounts of food which the human organism is able to absorb. This has been demonstrated for several food constituents such as fat, the absorption of which is still normal at a daily intake of some 600 g (460), and for protein, of which amounts up to 600 g/day can likewise be absorbed (701). Perhaps the large surface area of the small intestine should be viewed as a vestige of man’s remote past, when meals were less regular and food was taken when the hunt was successful, often after a fast of several days.

Special Forms of Sprue

Patients with coeliac sprue show per definition both a distinct clinical and biochemical improvement after gluten withdrawal. In addition the lesions of the small intestine in these patients should improve. In the characteristic case this improvement — particularly that in clinical symptoms — ensues rapidly and ultimately becomes a complete remission. Rubin et al. (736) maintain that complete remission occurs per definition in every coeliac patient on a strict gluten-free diet.

Pathophysiology of Coeliac Sprue

It is widely known that coeliac sprue is nearly always accompanied by malabsorption, and there are abundant relevant data on this subject. Far less attention has so far been paid to possible changes of the physiological processes in the small intestine in patients with coeliac sprue. There are indeed some indications that these processes take an abnormal course. This is quite conceivable, because the inflammatory lesions in the intestinal wall do involve mucosal and submucosal elements other than the enterocytes, such as the hormone or mucus producing cells, the nerve fibres and the blood vessels or lymphatics.

Morphology of the Small Intestine Under Normal Conditions and in Coeliac Sprue

In the small intestine as in nearly every other organ, form and function are related. And in this case, too, interaction is bidirectional. On the one hand, the function of the small intestine is determined by its structure, and on the other hand the structure of the small intestine seems to be subservient to the function which this organ is expected to fulfil. This interdependence prevails in normal circumstances as well as in diseases. For a better understanding of the function of the small intestine, we believe it is useful first to present a few remarks on the architecture and structure of the small intestine, and on the changes to which they are subject in patients with coeliac sprue. It is not our intention to give a detailed description of the morphology of the small intestine. More detailed data can be found in textbooks on anatomy or in other publications (775, 783, 857).

Physiology of the Small Intestine

Food, once ingested, becomes fragmented by chewing and mixed with saliva to facilitate swallowing. Saliva contains the enzyme α-amylase, which degrades the starch in the food. After passing through the oesophagus the food bolus enters the stomach, where it is further kneaded by vigorous contractions of the gastric wall and mixed with gastric juice, which contains pepsinogens and hydrochloric acid. The secretion of gastric juice is regulated by nervous and hormonal factors, especially by gastrin. The stomach serves as a temporary store for the food ingested. By periodic relaxation of the pyloric muscle, small amounts of the chyme are passed into the duodenum. The mode of evacuation of the stomach is dependent on the volume of stomach contents, the osmotic pressure and fat content of the meal, and the acid concentration (192). In addition to nervous reflexes, intestinal hormones probably also play an important role in the evacuation of the stomach.

Clinical Course and Response to Treatment

Before dealing with the treatment of coeliac sprue, it may be useful to discuss briefly the natural history of the disease. This seems to be particularly important with a view to a more accurate assessment of the effect of the gluten-free diet.