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3. small anirn. Pract. Vol. 8, 1967, pp. 123 to 130. Pergamon Press Ltd. Printed in Great Britain.

Physiology of the Alimentary Tract in Relation to Diarrhoea*

A. CARLYLE Dejiartment of Physiology, University of Brisfol

Abstract-Criteria of diarrhoea are discussed. The general nature of alimentary processes are considered briefly and a more detailed description is given of the accretion of endogenous material within the lumen of the alimentary tract and of the activity of epithelial cells. Special features of the tract of the dog and cat are considered and examples given of the types of alimentary functional inadequacy associated with diarrhoea in these species.

I N T R O D U C T I O N IT IS not the purpose of this paper to present an overall account of the physiology of the alimentary tract but rather to select certain aspects which seem relevant to the understanding of the possible causes and consequences of diarrhoea. I n doing this it has not been thought necessary to confine exemplification to the dog and cat since many of the principles involved are of general applicability and not restricted to particular species.

An initial difficulty is in the definition of the term ‘diarrhoea’, since it is often used somewhat vaguely and to refer to different kinds of abnormality of the faeces or of the defaecation pattern. I t may connote an increase in the quantity of faeces passed per day, an increase in the frequency of defaecation, an increase in the fluidity of the faeces, or the presence of abnormal faecal constituents. All these features may be present together in exaggerated form, as in the type of ‘scour’ associated with primary or secondary infections of the small and large intestines, or the features may appear singly or in any combination. There is generally implied or assumed to be an abnormal loss of nutrient material. I n any particular case it may be important to distinguish between these different meanings because of the different implications as to cause and consequence.

An illustration of this is seen in the figures given in Table 1 relating to the effect of transferring cattle to spring grass after winter stall rations. The result would be described as diarrhoea by the criteria cf total faecal bulk or of fluidity, but not on the

*To be presented at the 10th B.S.A.V.A. Congress, 1967.

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124 A . CARLYLE

criterion of nutrient loss. Criteria of diarrhoea are of particular importance in species such as the dog and cat in which marked differences are found, as between one individual and another, of both faecal consistency and defaecation pattern.

TABLE 1. THE EFFECT OF NUTRIENT INTAKE ON THE WATER AND DRY MATTER CONTENT OF THE FAECES

IN CATTLE

Faeces (Kg/Day) Water intake (Kg/Day) Total Water Dry matter As water Concealed in food

Winter stall rations 20 14.7 5 . 3 52 19 Spring grass 34 31.0 3.0 51 33

From ROOK, J. A. F. and BALCH, C. C. (1962) 3. agric. Sci. 58, 103.

Where diarrhoea, in any of the senses considered above, occurs, it may be attributable either to a failure of alimentary function to deal efficiently with normal ingesta, implying some impairment or abnormality of gut function, or to the inability of a normal gut function to cope with the stress imposed by an abnormal type or amount of ingested material.

NORMAL G U T FUNCTION The primary function of the gut is that of assimilation; the ingestion of nutrient

material; its passage along the tubular tract with a gradual conversion of insoluble to soluble material; a reduction in molecular size, and an absorption of the products of this process through the mucosal epithelium so that they become available as meta- bolic substrates; substances not being rendered absorbable, and not being absorbed, are rejected as the residual material in the faeces. I n the simple-stomached carnivore the breakdown of ingested material is brought about principally by enzymes liberated into the lumen of the gut, usually as components of glandular secretions. Both the breakdown of material (digestion), and its removal (absorption), may be completed or limited by time, due to the movement of material through the system. These three aspects of alimentary function-digestion, absorption and rate of passage- are each, separately, controlled by a variety of mechanisms which are often linked to the quality and quantity of luminal material. There are, in addition, interactions between the separate aspects. Rate of movement through the gut is controlled by the state of activity of its smooth muscle. The activity and reactivity of the inuscle is largely conditioned by the distension of the gut by the luminal fluid bulk which is, in turn, largely determined by the balance between secretion and absorption. Both these processes act in two ways, directly and indirectly through the osmotic conse- quences of their activities. The effectiveness of the secretory and absorbative pro- cesses are in turn, through the time factor, dependent on the rate of passage of luminal contents as influenced by fluid bulk.

Thus, there is a highly integrated relationship between the different aspects of alimentary function determining the efficiency of the assimilatory process. This tends, in the normal course of events, towards a ‘homeostasis’ of gut function and a stabilization of its terminal phase, the formation of faeces. I t is, however, a relation- ship in which abnormalities of faeces may be attributable to a variety of causes which

T H E A L I M E N T A R Y T R A C T I N R E L A T I O N T O D I A R R H O E A 125

may be late or early in the sequential chain, and which may take on an ‘escalatory’ character.

Regional separation of gut function Even apart from the special features associated with fermentative processes,

which are not prominent in the dog and cat, there is a considerable separation of function within the alimentary tract. Enzymatic digestion occurs only to a limited extent in the stomach, is most intense in the duodenum, less so in succeeding parts of the small intestine, and is again reduced to a low level in the large intestine. Absorption also only occurs to a limited extent in the stomach. Although it occurs throughout the small and large intestine, there are considerable differences both in the intensity and the nature of the absorption mechanisms at different levels. Absorption of nutrient organic material is maximal in the small intestine, especially in the duodenum, and is virtually completed before the large intestine is reached.

Absorption of inorganic ions occurs in both small and large intestines. I n the duodenum, the intensity of secretory processes results in a net gain in both water and sodium, an increase in fluid bulk, and a rise in cation concentrations towards that of blood. I n the ileum, absorption and secretion tend initially to be balanced and then fluid bulk and cation concentration both fall (Hindle and Code, 1962). I n the large intestine, absorption of both water and sodium continues with a progressive reduction in total fluid volume. The osmotic pressure of luminal fluids becomes hypertonic half-way along the small intestine, is isotonic by the time the caecum is reached, and hypertonic beyond this (Van Weerden, 1961).

The character of the luminal fluid in the different regions of the tract differs very much. The nature of the fluid leaving any one region is determined partly by the nature of the fluid presented to it, partly by the activity of the epithelial and glandular elements within the region and partly by the rate of passage of luminal fluid through the region. The predominance of secretory processes in the duodenum cause a rise in volume and tonicity which must be redressed by ileal absorption of organic and inorganic substances, and by further absorption in the large intestine of water and electrolytes. The faeces-forming function of the colon is influenced not only by its own absorbative capacity and motor reactivity, but also by the nature and amount of the material presented to it from the small intestine.

TABLE 2. DAILY INTAKE AND POSSIBLE ALIMENTARY LOSS OF WATER AND ELECTROLYTES IS MAN

Water Electrolytes in mxq. (1.) Na+ K+ HC03-

Daily intake 2 150 100 Alimentary secretions 8 600 50 net 900* Total ‘at risk’ 10 750 150 900 f ‘At risk’ as yo E.C.F. 125 62 400 380

“Excess over hydrion secretion.

Modified froin THOMPSON, R. H. S. and KINC,.J. (Eds.) (1964) Biochemical Disorders in Human Disease 2nd ed. Churchill, London.

126 A . C A R L Y L E

Luminal accretions Luminal contents represent much more than ingested material. There is a

considerable admixture of endogenous material. An obvious contribution comes in the form of the secretions of the various glands associated with the alimentary canal, and of the cells in the epithelium lining the gut itself.

From the figures given in Table 2 it is clear that water and ions in the luminal fluid are only in part derived from the ingested material, that the endogenous accretion is large in relation to the ingested component and, also, that it is large in relation to the immediately available reserve in the extra-cellular fluids. In so far as the luminal contents are ‘at risk’ (should absorption and re-absorption not occur under diarrhoea1 conditions) there may be not only a loss of potential nutrients but also a drain of body constituents, with dehydration, loss of electrolytes, and a loss of alkali reserve.

Nor is it only water and electrolytes which pass into the lumen with the secretion. Either in the form of mucus or of digestive enzymes there may be a considerable organic content. In man, pancreatic juice alone can account for as much as 10-20 g protein a day, compared with a recommended dietary protein intake of 70 g per day (Bell et al., 1965).

The second, and probably more important, source of luminal accretion is due to the desquamation of cellular material from the epithelial lining of the tract. There is a continual and rapid replacement of the cells of the epithelium, as is indicated in Table 3.

TABLE 3. RATES OF TURN-OVER OF CELLS

Time for complete turn-over, in days.

Tracheal epithelium Epidermis Bone marrow Gastric epithelium Duodenal epithelium

47.6

1.4-6.5 1.8-6-5

13-100

0.7-2.3

From LeBlond and Walker (1956).

LeBlond and Walker (1956) have estimated that in man, cell desquamation may represent the addition of 250 g protein a day to the luminal pool, representing a fourfold dilution of ingested protein. Nasset and Ju (1961), using labelled casein, round a fourfold dilution in the dog and a more than sixfold dilution in the rat, while Bolton (1964) has presented figures for the chicken indicating a dilution of dietary protein by a factor of between 8 and 54, depending on the proportion of cellulose in the diet. Cell desquamation, and the associated cell proliferation, occurs at a high rate throughout the alimentary tract, but is most intense in the small intestine. In this region, cell division is normally localized in the crypts of Lieberkuln (Plate, 1961), the newly formed cells miLgrating upwards over the surface of the villi, being shed at the tips. During this movement there may be a progressive differentiation of the epithelial cell and a loss in absorbative function (Kaneko et al., 1965).

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Failure of absorption and resorption may thus result in gross loss of body protein, as well as of body water and electrolytes.

Cellular activity By a number of criteria, the metabolic activity of the alimentary epithelial cell,

especially of the small intestine, is amongst the highest of any of the cells of the body Spencer and Knox ( 1960) quote QCB values of 22 - 7 for duodenum and 10.0 for ileum, as compared with 10 for liver; and a citric acid content of 7 - 7 mg/100 g tissue for the small intestine as compared with values of 2-4-5-1 for kidney, and 1.2-2-3 for liver. Platt (1961) found the rate of incorporation of labelled lysine by the intes- tinal mucosa to be higher than that of any other tissue studied, whilst the turnover rate of DNA is higher than that of the liver.

This intense activity is in part associated with the secretory and proliferative activities already noted, but is also in part associated with the process of absorption. Smythe (1963), in a recent review, has pointed out that for most, if not all, of the substances absorbed in the small intestine, there are active energy-consuming translocation mechanisms. The same author has also pointed out that the special development of mechanisms for the translocation of materials away from the luminal border of the epithelial cell must prevmt nutrient material reaching this area fi-om the mesenteric artery, so that a t least the luminal border of the cell is dependent upon luminal nutrients for its metabolism. The absorbative function of the cell is thus dependent upon thc luminal availability of nutrient material. Such a dependence may underlie the depression of protein utilization a t a low net-protein dietary intake described by Payne (1965) in the dog, as well as the nutritional diarrhoea in dogs on low protein diets, especially in con.junction with infestation with Toxocara canis, described by Heard (1965).

T h special position of t h dog and cat Compared with many other speciq the alimentary canal of the carnivore is

small. The contained ingesta may be as little as 4 per cent of total body weight, compared with as much as 25 per cent in the ruminant; the surface area of the gut is small by comparison with skin surface area, taking this as a parameter related to total metabolic rate; the length of the intestine is small in relation to that of the body. From the figures of Colin, quoted by Dukes (1955a), it may be calculated that, whereas the capacities of the stomach, small intestine and large intestine are in the proportions of 4- 3 : 1 : 1.4, their length are in the proportions of 1 : 6 : 1. Luminal contents must, therefore, be moving rapidly through the small intestine, and are present in this region of most intense digestion and absorption for only a small proportion of the time from ingestion to elimination. Moreover, this total time is itself short in these species. In this connection, the end to end nature of the junction between the ileum and colon in the dog, and the presence of a transient physiological pressure barrier rather than an anatomical sphincter (Kelly et al., 19651, may be of significance. The efficiency of absorption in the small intestine of the dog is, at least in some respects, low as compared with either the rat or the chicken (Dukes, 1955b).

By contrast with the herbivore, the dog and cat have a similar degree of depen- dence on the luminal pool of endogenous and exogenous nitrogen as that described

128 A. C A R L Y L E

by Bolton (1964) for the fowl, in that the ability to store amino acids is very limited; those not required for protein production being rapidly deaminated, so that the passing of large amounts of endogenous nitrogen into the gut may be regarded as creating a metabolic pool of amino acids. B-vitamins are also poorly stored and the metabolic pool is again largely in the gut.

These features suggest an unusually high endogenous investment in the luminal pool coupled with a low reserve capacity of absorbative function, and a potential instability of gut function.

INADEQUACIES OF G U T FUNCTION ASSOCIATED WITH DIARRHOEA IN T H E DOG A N D CAT

Abnormal loading of th gut Diarrhoea following the ingestion of excess dietary lactose, in both the dog and

cat (Anonymous, 1965) probably represents an osmotic loading of the small intestine resulting in the presentation of excessive fluid bulk to the large intestine.

Excessive motor activity This has been associated with diarrhoea in the dog (Joshua, 1963). I t may

represent a combination of stimulation by abnormal luminal conditions with some abnormality in the autonomic control of activity and reactivity of the musculature (Daniel, 1965).

Dcjiciency of digestive enzymes This may cause diarrhoea either by simple increase in non-absorbed material or

by raising luminal osmotic pressure. Steatorrhoea has been described in the dog resulting from deficiency of bile secretion (Knoebel and Ryan, 1963), or of pan- creatic secretion (Cohen and Annegers, 1953). Although fat slows the passage of luminal contents from the stomach to the small intestine (Antia et al., 1951), by raising fluid bulk in the small and large intestine, it increases passage-rates in these regions, thereby reducing the utilization of other dietary components. Pancreatic deficiency also results in enhanced faecal nitrogen losses and may be associated with coprophagy (Cohen and Annegers, 1953).

Impaired absorbative capacity This may result from a specific interference with cell proliferation, as appears

possible in feline panleucopaenia (Johnson, 1964; 1965), or follow a limitation of luminal nutrition of the epithelial cell (Payne, 1965). Nutritional failure of the epithelial cell may be associated with parasitic infestation (Heard, 1965; Ewing and Bull, 1966). I t may also be caused by the presence of a specific toxic substance, as could be the case in lead-poisoning (Wilson and Lewis, 1963), or the absence of a particular nutrient such as niacin in the cat (Heath et al., 1940). In this last respect the cat is peculiar in being unable to synthesise niacin adequately from dietary trytophan (Da Silva et al., 1952). An interacting combination of impaired absorba- tive capacity and diminished luminal nutrition, with or without pancreatic insuffi- ciency, may be present in cases resembling idiopathic or non-tropical sprue. (Himes and Adlersberg, 1958; Vernon, 1962).

T H E A L I M E N T A R Y T R A C T I N R E L A T I O N T O D I A R R H O E A 129

Impaired epithelial function is also found in many viral and bacterial infections of the intestine, whether with obvious lesions as in eruptive dog pox (Joshua, 1963), or at a subclinical level. Sprinz (1962), studying the foetal, normal adult, and germ- free adult pig, suggested that even in the 'normal' animal there were morphological and histological modifications of the intestinal epithelium, accompanied by functional impairment, which represented a physiological inflammation accentuated by infection.

REFERENCES ANONYMOUS (1965) Basic Guide to Canine Nutrition. Gaines Dog Research Centre, New York. ANTIA, F., ROSIERE, C. E., ROBERTSON, C. and GROSSMAN, M. I. (1951) Effect of vagotomy on gastric

secretion and emptying time in dogs. Am. 3. Physiol. 166, 470. BELL, G. H., DAVIDSON, J. N. and SCARBOROIJGH, H. (1965) Textbook of Physiology and Biochemistry,

6th ed., p. 277. Livingstone, Edinburgh. BOLTON, W. (1964) The nutritional significance of the endogenous nitrogen secretion in poultry.

In Symposium ofC.Z.O.M.S., (Ed. MUNRO, H. N.), pp. 117-122. Blackwells, Oxford. COHEN, B. J. and ANNEGERS, J. H. (1953) Faecal loss of various dietary nutrients in dogs lacking

pancreatic juice. Gastroenferology, 25, 67. DANIEL, E. E. (1965) The electrical and contractile activity of the pyloric region in dogs and the

effects of drugs. Gastromfmology, 49, 403. DUKES, H. H. (1955a) 7hC PhyJioloogy of Domesticukd Animals, 7th ed., pp. 300-301. BailliPre, Tindall

8c Cox, London. DUKES, H. H. (1 955b) The Physiology of Domesticakd Animals, 7th ed. , p. 451. Baillitre, TindalI & Cox,

London. Ewsc, S. A. and BULL, R. W. (1966) Severe canine diarrhoea associated with Balantidium-Trichuris

infection. 3. Am. vet. med. AS. 149, 519. HEARD, C. R. C. (1965) The effects of the protein values of diet and of Toxocaru canis infestation on the

digestion and utilisation ofprotein and cartmhydrates. In Symposium of B.S.A. V.A., (Ed. GRAHAM- JONES, O.), pp. 47-58. Pergamon Press, Oxford.

HEATH, M. K., MCQUEEN, J. W. and SPIES, ?'. D. (1940) Feline pellagra. Science N.2'. 92, 514. HIMES, H. W. and ADLERSBERG, D. (1958) Pathological changes in the small bowel in idiopathic

HINDLE, \V. and CODE, C. F. (1962) Some diflerences between duodenal and ileal sorption. Am. 3.

JOHNSON, R. H. (1964) Isolation of a virus from a condition simulating feline panleucopaenia in a

JOHNSON, R. H. (1965) Feline panleucopaenia. 11. Some features of the cytopathic effects in feline

JOSHUA, J. 0. (1963) The clinical approach to abdominal diseases of the dog. Vet. Rec. 75, 1269. KANEKO, J. J., MOULTON, J. E. BRODY, R. S. and PERRYMAN, V. D. (1965) Malabsorption syndrome

resembling non-tropical sprue in dogs. 3. Am. vet. med. Ass. 146, 463. KELLY, M. L. Jr., GORDON, E. A. and De WESSE, J. A. (1965) Pressure studies of the ileocolonic

junction zone of dogs. Am. 3. Physiol. 209, 333. KNOEBEL, L. K. and RYAN, J. M. (1963) Digestion and mucosal absorption of fat in normal and bile

deficient dogs. Am. 3. Physwl. 204,509. LEBLOND, C. P. and WALKER, B. E. (1956) Renewal of cell populations. Physwl. Rev. 36, 255. NASSET, E. S. and Ju, J. S. (1961) Mixture of endogenous and exogenous protein in the alimentary

tract. 3. Nuts. 74, 461. PAYNE, P. R. (1965) Assessment of the protein values of diets in relation to the requirements of the

growing dog. In Symposium of B.S.A.Y.A., (Ed. GRAHAM-JONES, O.), pp. 19-32. Pergamon Press, Oxford.

sprue; biopsy and autopsy findings. Gastroenferology, 35, 142.

Physiol. 203, 2 15.

leopard. Vet. Rec. 76, 1008.

kidney monolayers. Res. vet. Sci. 6 , 472.

PLATT, B. S. (1961) Digestion in infancy. Fedn. Proc., Fedn. Soc. exp. Bid. 20, 188.

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DA SILVA, A. C., FRIED, R. and DEANGELIS, R. C. (1952) The domestic cat as a laboratory animal for experimental studies. 111. Niacin requirements and tryptophan metabolism. 3. Nuutr. 46,399.

SMYTHE, D. H. (1963) Intestinal absorption. In Rccmt Advances in Physwlogy (Ed. CREESE, R.), pp. 36-68. Churchill, London.

SPENCER, R. P. and KNOX, W. E. (1960) Comparative enzyme apparatus of the gut mucosa. Fedn Proc., Fedn SOC. cxp. Biol. 19,886.

SPRINZ, H. (1962) Morphological response of intestinal mucosa to enteric bacteria and its implication for sprue and Asiatic cholera. Fedn Proc., Fcdn SOC. cxp. Bid. 21, 57.

VERNON, D. F. Jr. (1962) Idiopathic sprue in a dog. 3. Am. vet. med. Ass. 140, 1062. VAN WEERDEN, E. J. (1961) The osmotic pressure and the concentrations of some solutes of the

intestinal contents and faeces of the cow in relation to the absorption of minerals. J. ugric. Sci. 56, 317.

WILSON, M. R. and LEWIS, G. (1963) Lead poisoning in dogs. Vet. Rcc. 75, 787.

RCsumGLes crittres de Ia diarrhte sont discutk. La nature gtntrale du proctdt d’alimentation est brkvement considtrte et une description plus dttaillte est donnte de l’accroissement du mattriel endogtne dans le passage du systtme alimentaire et de l’activitt des cellules tpithtliales. Les traits sptciaux de ces regions chez le chien et le chat sont considtrk et des exemples sont prtsentes des types d’insuffisance fonctionnelle associte B la diarrhte chez ces espCccs.

Zusammenfassung-Besprechung der Merkmale von Diarrhoe. Die breiten Grundziige des Verdauungsprozesses werden k u n erwogen; eine mehr auf Einzelheiten eingehende Beschreibung des organischen Wachstums von endogenen Stoffen innerhalb des Hohlraumes im Verdauungskanal und der Funktion der Epithelzellen wird gegeben. Besonden charakteristische Merkmale des Vcrdauungskanals von Hunden und Katzen werden in Betracht gezogen sowie Beispiele der Abarten von funktioneller Insuffizienz, welche bei diesen Tiergattungen mit Diarrhoe assoziiert ist, gegeben.