11 March 1967 BmRISH

MEDICAL JOURNAL 613

Current Practice
MEDICINE IN THE TROPICS

Malabsorption
G. C. COOK,* M.D., B.SC., M.R.C.P.

Malabsorption implies a defect in the absorption of one or more severe case steatorrhoea (Gk. stear fat, rhoia flux) is usually,
nutritive substances, due to an abnormality either in the intestine but not always, present. Diarrhoea is usual, with voluminous,
or in one of the digestive organs. Impaired absorption of pale, frothy, foul-smelling stools which have a porridge-like
several substances, such as fat, protein, fat-soluble vitamins, consistency. They tend to float, and are often not easily
vitamin B12, folic acid, and iron, is often present (Table I). flushed from the lavatory. A bloated abdomen, excessive flatus,
Selective malabsorption of a single substance may, however, and gross weight loss are other features of the condition. In
occur, as in vitamin-B12 malabsorption in pernicious anaemia the less severe cases malaise, general ill-health, and dyspepsia
or disaccharide malabsorption in disaccharidase deficiency. resembling peptic ulcer are common, as are mental apathy and
Malabsorption syndromes are present throughout the world. depression, and at first the patient may be thought to be suffer-
The main causes tend to be different numerically in tropical ing from a psychiatric disease. Patients frequently complain of
zones compared with temperate zones. As work in the field symptoms referable to anaemia, osteoporosis, osteomalacia, and
increases, however, it becomes abundantly obvious that the vitamin deficiencies, and many are found to have recurrent
geographical distribution of aetiological factors is not as clear- glossitis with a sore raw-looking tongue or aphthous ulceration.
cut as was formerly supposed. Bone pain and failure in the healing of fractures are sometimes
encountered. Tetany may also be present. Nocturnal diuresis
TABLE I.-The Results of Defective Absorption of Various Dietary and hypothermia occasionally occur. In cases due to chronic
Substances
pancreatitis the main complaints may be of abdominal pain
Fat Steatorrhoea, weight loss radiating to the back, polyuria, and polydipsia. An example
Carbohydrate Flatulent dyspepsia, abdominal distension of a patient with chronic pancreatitis and severe malabsorption
Protein Wasting, oedema
Folic acid Macrocytic, megaloblastic anaemia,
is shown in Figs. 1 and 2. The syndrome should be included
glosastis in the differential diagnosis of every case of iron-deficiency
Water- Vitamin B1s Macrocytic, megaloblastic anaemia, anaemia which fails to respond to iron after elimination of
Soluble glossitis, neuropathy
Vitamins Vitamin-B complex Cheilosis, angular stomatitis, dermatitis
polyneuritis
hookworms, and in all cases of macrocytic (megaloblastic)
Vitamin C Bleeding tendency anaemia, due to either folic-acid or vitamin-B,2 deficiency.
Fat- Vitamin A Follicular hyperkeratosis, xerophthalmia Signs are often few and rarely give much help in diagnosis.
Soluble Vitamin D & calcium Skeletal changes, tetany The muscle mass is diminished, often grossly, and there is loss
Vitamins i Vitamin K Purpura, haemorrhages
of subcutaneous tissue. The hair is soft, often sparse over the
Iron Hypochromia
Sodium Muscular weakness, cramps occipital region, and lacks its usual elasticity. Cheilosis,
Potassium Flaccidity, arrhythmias angular stomatitis, and glossitis are often present. Hyperkera-
Magnesium Muscular weakness
Water Nocturnal diuresis totic skin changes, often accompanied by hypopigmented patches,
are common. Iron-deficiency anaemia may be present, but this
is widespread in the tropics owing to other causes. Signs which
Until recently the malabsorption syndrome was thought
very are present in some cases include oedema, finger-clubbing,
to be rare throughout tropical Africa. Malabsorption in the splenomegaly, pigmentation, and hypotension. Evidence of
tropics was formerly equated with tropical sprue. Many other vitamin deficiencies is often present. There are no signs
cases present with the florid symptoms outlined below. Many which give a clear-cut distinction from protein-calorie
less severe cases exist, however, and present in less dramatic malnutrition.
ways. As most of the signs and symptoms of malabsorption In children the picture may be very similar to that in the
are a result of malnutrition, this is the main differential diag-
adult. In protein-calorie malnutrition, especially kwashiorkor,
nosis. Severe malnutrition causes damage to the absorptive part of the clinical picture is due to failure of absorption from
areas of the small intestine, and the two conditions may be the severely damaged small-intestinal mucosa; pancreatic dys-
coexistent. Any condition producing diarrhoea and severe function is also present. Failure to grow is common, and weight
small-intestinal hurry will be accompanied by some degree of is affected more than height. There is muscular wasting and
malabsorption. Such conditions are common in tropical hypotonia. The child is often fretful and irritable. The eyes,
regions and often have a bacterial or virus origin. face, hands, and feet may be puffy, and there may be oedema of
the penis and scrotum. The abdomen is distended and the
hair is depigmented and becomes brown or straw-coloured.
Clinical Presentation The skin may be coffee-coloured with reddish-brown areas
A detailed dietary history must always be obtained, especially instead of its usual black coloration. Circumoral pallor may
be present and there is a generalized thickening and flaking
to exclude malnutrition, as the clinical signs in the two condi- of the skim
tions are often very similar. This may be very difficult in
indigenous populations owing to language difficulties. In the Other causes of severe weight loss should always be considered
in the differential diagnosis. Gastrointestinal signs and
* Lecturer in Medicine, Makerere University College, Kampala, Uganda. symptoms in the malabsorption syndrome are not always obvious
 BRITISH
614 1 1 March 1967 Malabsorption-Cook MEDICAL JOURNAL

on clinical examination. Low blood pressure, skin pigmenta- Disease of the Pancreas or Biliary System
tion, and muscular weakness may suggest adrenal cortical In Uganda, Nigeria, and probably throughout tropical Africa,
failure.
and possibly the Far East also, chronic pancreatitis accounts
for a high proportion of cases of chronic malabsorption. The
Aetiology presentation is usually either with gross weight loss and steator-
rhoea or with the symptoms of diabetes mellitus. Some cases
Table II gives the main causes of the syndrome. Although present with generalized oedema. In pancreatitis the main
many of these factors may be present in any area of the world, defect is in digestion, and though deficiency of fat-soluble
the causes particularly important in tropical countries are indi- vitamins may occur water-soluble vitamins are usually well
cated. Hitherto there has been a tendency to regard the syn- absorbed. Anaemia and deficiency of vitamin B,2 and folic acid
drome as a chronic one. It is now clear that it may take an are uncommon. Patients often complain of recurrent severe
acute form following, for example, acute gastroenteritis of upper abdominal pain, and parotid gland enlargement occurs
bacterial or virus origin. Malabsorption is transient in most in some; but parotid enlargement is in any case a frequent
such cases. In a few, however, a significant degree of mal- finding in some populations living in the tropics. The patho-
absorption may persist for weeks or months after the initial logical changes in the pancreas consist of fibrosis and lithiasis.
acute attack. There is increased iron absorption, which may lead to haemo-
siderin deposits in the liver. The disease may occur at any
time from childhood to late adult life and is possibly more
common in males. The cause is unknown; both malnutrition
and excess alcohol have been incriminated.
Throughout tropical Africa (East and West Africa, and the
Congo) gall stones are uncommon, and prolonged extrahepatic
obstructive jaundice does not seem to be as common as in
most temperate zones. Cases due to chronic pancreatitis or

carcinoma of the head of the pancreas are occasionally seen.

Prolonged intrahepatic cholestasis and transitory steatorrhoea
following cholestatic virus hepatitis or hepatotoxic agents does
not appear to be more prevalent than in temperate zones. Gall
FIG. 1.-The general appearance stones are common in some parts of the Far East.
of a 52-year-old Ugandan male
from the Baganda tribe with severe
chronic calcified pancreatic disease.
Daily faecal fat excretion was 16 g.
He also had moderately severe
diabetes mAlitus. Intestinal Causes
In the small intestine mucosal damage of any cause, diminu-
tion in the absorptive area, or alteration of the luminal milieu
int&ieur may produce the syndrome. Although minor mucosal
damage is often found in indigenous populations in many parts
of the tropics, this does not in most cases give rise to much
malabsorption, although D-xylose absorption may be impaired
in some otherwise healthy subjects. Biopsy specimens of the
mucosa contain many more leaf-shaped than finger-shaped villi
in patients from these areas ; the cause of this is not yet clear.

FIG. 2.-Straight x-ray of the ab-

domen of the same patient show-
ing extensive pancreatic calcifica- TABLE II.-Causes of Malabsorption Syndromes
tion. DEFECTIVE GASTRIC FUNCTION
Gastritis, peptic ulcer, ]
total gastrectomy, inadequate mixing; intestinal hurry.
FIG. 1 gastrocolic fistula.
DEFECTIVE DIGESTIVE GLANDS
* Pancreas-e.g., chromic calcified pancreatitis.
Liver-e.g., prolonged biliary obstruction.
LESIONS INVOLVING THE SMALL INTESTINE
Mucosal lesions
* Tropical sprue.
* Jejunitis, ileitis.
* Infiltrative lesions-e.g., tuberculous enteritis, Crohn's disease, Whipple's
disease, systemic sclerosis, leukaemia, reticuloses, amyloidosis, abnormal
lymph drainage.
* Enzyme defects-e.g., disaccharidase deficiencies.
Coeliac disease, adult coeliac disease (gluten-induced enteropathies).
* Resection of part of the small intestine (i.e., absorptive-surface deficiency).
Intraluminal abnormalities
* Parasites-e.g., Giardia lamblia, Strongyloides stercoralis, Diphyllobothrium
Ankylostoma duodenale.
latum,
Stagnant loops, strictures, fistulae, jejunal diverticulosis.
Vascular lesions of the small intestine
* Constrictive pericarditis.
* Endomyocardial fibrosis.

Congestive cardiac failure.

Superior mesenteric thrombosis.
IATROGENIC CAUSES
Neomycin, triparanol, phenindanedione, phenolphthalein, colchicine, para-amino
salicvclic acid, radiation.
ENDOCRINE DISORDERS
Addison's disease, hypoparathyroidism, diabetes mellitus, Zollinger-Ellison
syndrome.
MISCELLANEOUS CAUSES
Cystinuria, Hartnup disease, acanthocytosis, agammaglobulinaemia, pneumnatosis
cystoides, malignant carcinoid syndrome.
* Indicates causes which are more common n the tropics than .n temperate
FIG. 2 zones.
11 March 1967 Malabsorption-Cook BRIMSH
MEDICAL JOURNAL 615

Conditions in which the ileum is involved often have vitamin- will probably be suffering from a lack of intestinal mucosa, or
12 deficiency part ofthetheterminal
as
vitamin is confined to
clinical picture; absorption of this
ileum.
a structural abnormality.
The two most important parasitic diseases which can certainly
Tropical sprue was first described in the eighteenth century. cause malabsorption are caused by Giardia lamblia and
Until recently it was thought to be a chronic form of mal- Strongyloides stercoralis. The clinical picture in the latter
absorption occurring solely in expatriate subjects living in the condition may be associated with an irritating rash, pulmonary
tropics, but it is now known that acute cases are very common. symptoms, and an eosinophilia. Necator americanus almost
Sprue is widely found in many parts of the tropics, including certainly does not produce malabsorption. There is some evi-
the Far East, India, Indonesia, the West Indies, and South dence that Ankylostoma duodenale may be responsible in some
America. It is probably unusual in Africa, although only on cases. Tape-worms do not cause this syndrome.
rare occasions has it been looked for seriously. It has a charac- Cardiac lesions, especially constrictive pericarditis and endo-
teristic local distribution, occurs in epidemics, and may have myocardial fibrosis, are common in many areas of Africa and
a seasonal incidence. The mode of onset is variable. Anorexia, these may produce malabsorption by an indirect disturbance
lassitude, and diarrhoea are usual initially. Weight loss, of the vascular supply to the small intestine, though this has
glossitis, stomatitis, anaemia (usually megaloblastic), and other not yet been adequately investigated.
vitamin deficiencies follow. A pre-existing folic-acid deficiency is Adult coeliac disease and coeliac disease are the commonest
usual in most patients owing to an inadequate diet ; it is also often small-intestinal causes of malabsorption in Great Britain. They
seen after pregnancy. Folic-acid deficiency seems to be are probably related, since they are both precipitated by the
uncommon in the normal Ugandan and this may explain the
same factor-gluten. Adult coeliac disease occasionally occurs
rarity of tropical sprue here. It is probable that the syndrome in patients who have had coeliac disease in infancy. There is
is set off by an acute insult to the intestinal mucosa, such as increasing evidence that the two diseases are also by no means
acute gastroenteritis of bacterial, viral, or helminthic origin. In uncommon in both indigenous and expatriate populations in
the presence of a deficiency of folic acid, which is required for the tropics.
the rapid production of cells in the small-intestinal mucosa,
persistent damage and malabsorption result. It is possible that
the severity of the disease is dependent on the degree of folic- Investigations
acid deficiency; recently a correlation between the severity of
malabsorption and the degree of mucosal damage in acute cases There are no simple tests for differentiating protein-calorie
has been noted. In some, folic-acid deficiency may play only malnutrition from the malabsorption syndromes; in the former
a minor part, in which case the disease starts with a gastro- secondary mucosal damage is relatively common. Careful
intestinal infection and folic-acid deficiency follows. macroscopic inspection of the stool will often strongly suggest
Acute or subacute cases of jejunitis (enteritis necroticans), steatorrhoea. A gross excess of fat in the stool is unusual in
usually in children, have been reported in New Guinea and uncomplicated malnutrition.
Uganda. Presentation is as an acute episode with colic, diar- Urine examination may show glycosuria in patients with a
rhoea, and even melaena. There is segmental ulceration with pancreatic cause for the malabsorption syndrome. Haemato-
necrosis of the jejunum. Clostridium perfringens is the prob- logical investigation will reveal an iron-deficiency anaemia in
able pathogen. Death in the acute stage is usual, but a few very many patients in the tropics, but a macrocytic anaemia
survive long enough to suffer from malabsorption. due to folic-acid or vitamin-B12 deficiency or both may be caused
Tuberculosis of the small intestine (tabes mesenterica) by a malabsorption syndrome-e.g., tropical sprue. If it is
accounts for some cases of malabsorption in very many parts possible to perform a gastric test meal, the presence of free
of the tropics. acid will rule out pernicious anaemia and make malabsorption
a much more likely cause of the anaemia.
Estimation of faecal fat will only rarely be possible at up-
country stations. If this is possible a 72-hour collection in a
Lactase Deficiency patient receiving a normal diet containing 50-100 g. of fat
Digestion of disaccharides is dependent on the presence of daily should be done to establish the presence of steatorrhoea.
Daily excretion of more than 6 g. will indicate malabsorption.
disaccharidases in the mucosal cells of the small intestine. Microscopy of a random stool may be of value.
Discovery of widespread lactase deficiency in some populations
living in the tropics has led to the recognition of many cases A specimen of faeces is emulsified on a glass microscope slide
of diarrhoea which are occasionally accompanied by steatorrhoea, with ethyl alcohol and stained with alcoholic Sudan 3. In severe
pancreatic steatorrhoea large numbers of yellow or orange neutral
presumably due to intestinal hurry. The deficiency seems to fat globules may be seen; they may also occur, however, after
occur in some populations as an isolated, probably genetically liquid paraffin ingestion. If a specimen of stool in tropical sprue is
controlled, defect. It is common in Uganda and parts of the treated with 36% acetic acid and three times gently heated to boiling
Far East. In some Ugandan tribes a highl level of the enzyme point, soaps and glycerides are converted to free fatty acids which can
exists at birth, but this falls at varying times during the first also be demonstrated as spherical droplets with Sudan 3. Large num-
three or four years of life. Failure to thrive in infancy may be bers of fatty acid crystals may also be seen when there is gross faecal
caused by this defect in some cases owing to failure of absorp- fat loss, as in tropical sprue. Microscopy may also reveal undigested
tion of lactose, which constitutes about 50% of the calories in meat fibres in pancreatic disease. An absence of trypsin in the
breast milk. Lactase deficiency may also exist as part of a stool in severe chronic pancreatitis may occasionally be demonstrated
by placing a specimen of faeces on an exposed x-ray film; removal
general depression of disaccharidases when the jejunal mucosa of the black emulsion will not usually occur ; this test must, how-
is severely damaged, as in severe protein-calorie malnutrition ever, be interpreted with caution. Microscopic examination of the
or severe gastroenteritis. Other enzyme defects responsible for stool may also be of value in detecting intestinal infestations. Hook-
intolerance to certain foodstuffs will probably come to light in worm ova and larvae of Strongyloides should be found. In some,
the future. but not all, cases of Giardia lamblia infestation this is also helpful.
Massive small-intestinal resection involving much of the In cases of severe disaccharidase deficiency-i.e., when there
small intestine is frequently seen in some parts of Africa after is either a primary deficiency of lactase, or severe mucosal
either strangulated hernia, trauma, or volvulus of the intestine. damage-the appropriate disaccharides are not hydrolysed
The latter condition is common in some parts of tropical and an excessive amount of reducing substance may be
Africa. Survival is possible if only a few feet of small intestine detected in the stool. An approximate estimate is obtained by
remain. A patient with an abdominal scar and malabsorption the " Clinitest" technique. A specimen of liquid stool is
E
616 11 March 1967 Malabsorption-Cook BRIrTSH
MEDICAL JOURNAL

diluted with its own volume of water, and five drops of the slower and less spectacular response than folic acid. Both folic
suspension are mixed with ten drops of water and a " Clinitest " acid and antibiotics may be used in a severe case. Failure of
tablet in a test-tube. The result can be expressed as g. per response to folic acid and antibiotics may indicate that the
100 ml. stool. Amounts of 3 g. per 100 ml. stool may be diagnosis of tropical sprue is wrong. Tropical sprue does not
present in severe cases of disaccharidase deficiency, although the respond to a gluten-free diet. The long-term outlook is very
presence of any reducing substance is abnormal. In such cases good.
stool pH which can be measured with pH paper may be acid Where malabsorption is due to intestinal resection, if the
(less than pH 6.0) owing to the presence of lactic and other terminal ileum is involved, vitamin-B12 supplements will be
volatile fatty acids derived from bacterial action on the un- required, as this is the only site of absorption of this vitamin.
absorbed lactose and other disaccharides. It is often worth trying a gluten-free diet if this is possible,
If x-ray facilities are available straight x-ray of the abdomen as gluten-induced enteropathies (adult coeliac and coeliac
may reveal calcification within the pancreas in chronic pan- disease) undoubtedly occur in the tropics. The dietary restric-
creatic disease. This varies from fine disseminated calculi in tions must be very rigidly observed. Response may be delayed
the tail and body of the pancreas to larger discrete calculi which for up to six months after diagnosis. Some seem to be per-
may be so diffuse that the whole pancreas is outlined (Fig. 2). petuated by an abnormal bacterial flora, and broad-spectrum
In tuberculosis of the small intestine diagnosis may be facili- antibiotics are then of value. In a minority A.C.T.H. or
tated by finding evidence of tuberculosis in the chest x-ray or corticosteroids may be necessary to produce a remission, but
calcified lymph glands in the straight film of the abdomen. here careful supervision and constant awareness of the compli-
Other investigations may be required to reach a firm diagnosis cations of this form of treatment are required. Continuation
of the cause of malabsorption. These include oral glucose on a gluten-free diet throughout life is usually necessary.
tolerance, D-xylose absorption, tests of pancreatic function (e.g., In cases of lactose intolerance a non-lactose diet is required.
the secretin-pancreozymin provocation test), serum folate, Treatment must be rigidly carried out, for even small amounts
formiminoglutamic acid excretion, serum B52, and the Schilling of lactose in milk products will precipitate diarrhoea in a severe
test. A barium meal, radiology of the small intestine by small
bowel enema, and peroral jejunal and ileal biopsy are also of
great value. An augmented histamine test meal and a vitamin-A TABLE III.-Management of a Patient with Malabsorption
absorption test may be helpful. In long-standing cases estimation GENERAL PRINCIPLES
of the serum calcium and skeletal x-rays may reveal osteo- High-calorie, high-protein, low-fat diet.
malacia. Most of these tests, however, will be performed only (a) Replacement (during period of active malabsorption)
in large well-equipped hospitals, of which there are few in Tab. aneurin. co. fort. 1 t.d.s. Oral

20 mg. daily
tropical countries. Folic acid.
Vitamin B, . 100 jg. monthly Intramuscular
Ascorbic acid 50 mg. daily
Vitamin A. 4,000 i.u. daily Oral
D.. 10,000 i.u. daily
20 mg. daily ,9.
K (water soluble)
E 100 mg. daily
Management Ferrous gluconate. 10 g. daily
Calcium 15 g. daily

Table III gives a summary of the principles of management (b) Symptomatic

Mist. kaolin. et morphin. I fl. oz. t.d.s.
,

of a patient with the malabsorption syndrome. An accurate Codeine phosphate 30 mg. t.d.s. .,
diagnosis should if possible be made in all cases before treat- SPacrPIc TREATMENT
ment is started, and this will in very many necessitate transfer Chronic pancreatitis
Pancreatic extract, pancreatin B.P... 3 g. t.d.s. before meals
Oral
of the patient to a larger hospital with good diagnostic facilities. Insulin
or tolbutamide (to control diabetes
Subcutaneou-
As soon as diagnosis is reached management is usually fairly mellitus) Oral
straightforward. Tropical sprue
0-2 mg. daily (8 weeks)
During the phase of active malabsorption general replacement Folic acid
5 mg. daily
Intramuscular

therapy is indicated. A high-calorie, high-protein, low-fat diet (6-12 months)

100 ug. monthly
Oral

Vitamin B1s.
with adequate replacement of minerals and vitamins is necessary. (12 mor chs)
10 g. dai'1 (5 days)
Intramusculam
Symptomatic treatment may be necessary if diarrhoea is parti- Succinyl sulphathiazole
2 g. d sy (5 days)
Oral

cularly troublesome.
Chlortetracycline
Chloramphenicol 2 g. daily (5 days)
(consecutively)
3S
Pancreatic disease is difficult to manage and there is no cure.
Pancreatic extract (pancreatin B.P.) may be given orally before rarasites
meals, and increase in weight usually occurs. The diabetes Ankylostomiasis
Ferrous sulphate 0') mg. t.d.s. (continue
mellitus which often accompanies this disease is usually fairly for 3/12 after Hb is
normal)
easily managed either with insulin or occasionally with oral Bephenium hydroxynaphthoate 5 g. daily on empty
stomach (3 consecu-
hypoglycaemic agents. Some patients, however, require an (Alcopar)
tive days)
astonishingly high dose of insulin for stabilization. or tetrachlorethylene 4 ml. stat.
In tropical sprue initial treatment should be carried out in Strongyloides stercoralis
200 mg t.d.s. (21 days)
Dithiazanine
hospital. Spontaneous recovery may occur, although the overall or thiabendazole. 25 mg./kg body weight
mortality rate in untreated cases is very high. It was formerly (2 days)
thought that expatriates who contracted the disease had to be Giardia lamblia
100 mg. t.d.s. (5 days)
Mepacrine
moved to temperate climates. Recent evidence indicates that if (repeat after I week
a satisfactory cure is obtained recurrence is unusual even if the if stool still positive)
or metronidazole. 200 mg. t.d.s. (7 days)
patient is left in the tropics ; there is as yet, however, no really Lactose intolerance
satisfactory follow-up study available. Most cases respond to Lactose-free diet.
folic acid alone (Table III). Response is usually dramatic, often Milk, creams, ice-creams, milk powder, etc., must be excluded.
Commercial yoghurt may contain some lactose (lactose is not
in the first few days, and the megaloblastic anaemia improves hydrolysed by boiling)
immediately; the intestinal mucosa returns to normal in 12-18 Gluten-induced enteropathy (adult coeliac disease, coeliac disease)
months. Owing to involvement of the ileum in tropical sprue Avoid all foods containing even traces of wheat or rye gluten
indefinitely. Very many commercial foods, sweets, ice-creams.
(unlike adult coeliac disease), if folic acid is given and vitamin etc., contain wheat gluten. (A list of suitable foods is given
in many textbooks of medicine.) Corticosteroids may be
B12 is not, cases of subacute combined degeneration of the cord required in a few cases (e.g. prednisone, 10-15 mg. daily)
may be encountered. Broad-spectrum antibiotics produce a
11 March 1967 Malabsorption-Cook BRITCUH 617
case. In the secondary forms treatment can be discontinued of the tropics may lead to the more adequate treatment of
as the mucosa recovers and lactase reappears. some cases of diarrhoea and malabsorption. It is most important
to exclude other causes, such as those commonly seen in tem-
Summary and Conclusions perate zones, for only by systematic exclusion will it become
clear which are the truly common causes in any locality.
Malabsorption syndromes are common in the tropics; the A full clinical history and examination, together with a simple
causes have a definite geographical distribution. Protein- haematological, biochemical, and radiological examination, will
calorie malnutrition is the commonest and often most difficult allow a reasonable diagnosis in some cases. Careful macro-
differential diagnosis. Common causes in temperate regions scopic inspection of the stool is of very great importance, though
(e.g., adult coeliac disease and coeliac disease) seem to be less malabsorption may be present without gross abnormalities. In
common, but there is evidence that this is merely because they many cases it is impossible to arrive at the exact cause of the
have not been properly looked for. In Africa chronic calcified syndrome unless the diagnostic facilities of a large hospital are
pancreatic disease is undoubtedly a more common cause than available. Treatment is often simple and can easily be main-
in most temperate areas, and in the Far East tropical sprue tained at up-country stations when the diagnosis has been made.
accounts for many cases. Recent demonstration of disacchari- It is essential to consider the entire differential diagnosis in
dase deficiencies-either primary or secondary-in several parts every case.

TODAY'S DRUGS
With the help of expert contributors we publish below notes the coronary blood flow in patients whose vessels are damaged
on a selection of drugs in current use. by atheroma, and whose vessels are already maximally dilated as
a result of local tissue hypoxia. It is therefore misleading to call
nitroglycerin and other similar drugs coronary vasodilators. It is
Nitrites and Nitrates in the Treatment of also unlikely that these drugs will stimulate the development
Ischaemic Heart Disease of a collateral circulation, and, indeed, proof of any beneficial
effect in promoting the development of such collateral vessels
Ischaemic heart disease or coronary failure results when the in patients with coronary artery disease is lacking.
supply of oxygenated blood through the coronary arteries is
inadequate to meet the demands of cardiac muscle. Occlusive
disease of the coronary vessels is nearly always the result of Long-acting Compounds
atherosclerosis. This is a disorder affecting large arteries in
which fatty deposits and fibrous nodules narrow the lumen of The effects of nitroglycerin and amyl nitrite, though bene-
the artery, reduce the potential blood flow, and predispose to ficial for the acute attack of angina, are short-lived, and attempts
intravascular thrombosis and the clinical syndrome of angina have been made to produce drugs with a prolonged action.
of effort. Many preparations have been marketed claiming to be long-
At rest there is little difference between the rate of coronary acting coronary vasodilators, but not only do they have no
blood flow in the normal subject and in the patient with vasodilating effect on the diseased coronary arteries but none
coronary artery disease. However, a normal individual can has been shown to have any greater effect on angina of effort
increase his coronary blood flow severalfold, but the patient than a placebo.
with coronary artery disease is unable to do so, and indeed The problems of assessing these drugs are great. Objective
may not even be able to increase the resting blood flow at all. evaluation of changes in the coronary circulation is difficult.
The normal coronary circulation delivers more blood to the Coronary arteriography cannot give the conclusive evidence,
as even if an increase in the calibre of coronary arteries is
myocardium on demand, and the strongest physiological demonstrated this does not prove that there is an increase in
stimulus to coronary vasodilatation is hypoxia. Angina of effort blood flow, as the smaller arterioles cannot be visualized, and
develops only when there is severe myocardial hypoxia as a these are the vessels that regulate blood flow. If isotope studies
result of inadequate perfusion, and, under these circumstances, of coronary blood flow demonstrate an increase, this does not
the affected coronary vessels are already under the maximum indicate that the increase in flow is to the ischaemic area.
physiological stimulus to dilate. Indeed, this is unlikely, as the diseased vessel is probably not
able to dilate further. The electrocardiogram is often used as
an objective measure of the patient's exercise tolerance, but even
Nitroglycerin and Nitrites this has pitfalls, as repetitive tests are executed with decreasing
The drug that betters this physiological dilating mechanism effort and anxiety.
does not exist. However, the beneficial effects of nitroglycerin These objective methods do not measure angina. Angina
(glyceryl trinitrate) in angina of effort are undoubted, and is a syndrome which cannot be measured objectively. Sub-
indeed have been known for over 100 years, but this is not the jective methods are therefore essential to the clinical assessment
result of coronary vasodilatation. of therapeutic agents, and only the controlled trial can determine
The basic pharmacological property of nitrites is to relax the efficacy of a new drug.
smooth muscle, and it is the effect on vascular smooth muscle A large proportion of patients with angina improve on
that is particularly relevant to the patient with ischaemic heart placebo therapy. The knowledge that they are involved in a
disease. The major effect of nitrites is on the small postcapillary test of a potentially effective treatment reduces the incidence
vessels. As a result of relaxation of the smooth muscle of these of angina in 50% of cases. Anxiety stimulates the sympathetic
vessels the mean systemic arterial blood pressure falls, and this innervation of the heart and brings about the release of endo-
reduces the oxygen requirements of the heart usually to a level genous noradrenaline, which increases the oxygen requirement
which can be adequately supported by the unaltered coronary of the heart by increasing cardiac work and metabolism. Any
blood flow. While it is true that nitroglycerin dilates the drug given with enthusiasm will allay anxiety, and will there-
coronary arteries of normal human beings, it does not increase fore improve the patient's symptoms. It is thus essential that