Anaemia

ANAEMIA, a generic term for various forms of disease characterized by a defective constitution of the blood, or, more specifically, by a reduction in the oxygen-carrying power of the blood. This reduction is due, either to a decrease in the number of red blood corpuscles, or to a decrease in the amount of haemo globin they contain, haemoglobin being that constituent of the red corpuscles which makes it possible for them to carry oxygen to the tissues and to play an important role in the transfer of carbon dioxide from the tissues to the lungs. The amount of haemoglobin that each red corpuscle contains is represented by a term known as the colour index, which is derived by dividing the percentage of haemoglobin by the percentage of red corpuscles.

Types of Anaemia.

Thecustomary division is as follows: (a) the primary, those in which the cause is yet unknown; and (b) the secondary, those due to some known cause. Chlorosis and pernicious anaemia are primary anaemias. The anaemia caused by haemorrhage, malaria, chronic poisoning by known chemical and biological agents, parasites, malnutrition, malignant disease, etc., is secondary.

Symptoms.—Sincethe chief derangement in all anaemias is a reduction of the total amount of haemoglobin in the blood, the symptoms and pathological anatomy are quite similar in the dif ferent kinds of anaemia. Pallor of the skin and mucous mem branes, shortness of the breath, palpitation, faintness, weakness, languor, headache, and usually gastro-intestinal disturbances, are the general symptoms. A special tendency to haemorrhage is fre quently present. The physician frequently finds the heart to be dilated and hears systolic murmurs in the heart on auscultation. Anatomically the internal organs are pale, sometimes smaller than normal and atrophic, and their cells contain an excessive amount of fat. The spleen is enlarged in some anaemias and is usually denser than normal. The red bone-marrow, which forms the red corpuscles and haemoglobin, is increased in amount except in rare cases. The diagnosis depends on the clinical picture, the examina tion of the blood, and a number of other findings.

Causative Factors.

Obviously anaemia must be due to either one or a combination of the following factors : loss of blood, in creased destruction of red corpuscles, or a disturbance of the red bone-marrow (erythroblastic tissue), leading to a decrease in the normal supply of red corpuscles or to a decrease in the amount of haemoglobin they contain. The red bone-marrow in health con tinually supplies the blood with red corpuscles which contain a constant amount of haemoglobin to take the place of those de stroyed in the liver, spleen and other tissues ; so that the number of red corpuscles and the total amount of haemoglobin in the blood remain constant.

If blood is lost, or if there is an increase in the destruction of red corpuscles, the red bone-marrow compensates by producing red corpuscles at a more rapid rate than normal. In such a case, especially if the loss, or destruction, is great, the red corpuscles so produced are frequently small, contain a subnormal amount of haemoglobin and may even contain a nucleus, which denotes that the cell is young. In the course of time these abnormal cells are replaced by normal cells and the red bone-marrow returns to a normal rate of production. But if the loss or destruction is con tinuous or intermittent, as in chronic anaemias, the blood contains more and more abnormal red corpuscles. The erythroblastic tissue further attempts to compensate for this continuous demand for red cells by invading and replacing the yellow marrow which does not form red corpuscles. If the demand is in excess of the capac ity of the erythroblastic tissue to respond, the condition of the blood seen in the chronic anaemias develops, namely, a decrease in the number of red corpuscles, the presence of abnormal types of corpuscles, and a diminution of the total amount of haemo globin in the blood.

In some of the anaemias it is possible to state definitely which of the above factors are concerned ; in others opinion can be based only upon an interpretation of the known facts. In the anaemia that follows repeated haemorrhage, as occurs in ulcers of the gastro-intestinal tract, the obvious factor is the loss of blood. In the anaemias caused by haemolytic toxins, the destruc tion of red corpuscles is the chief factor concerned, although these toxins may also act on the erythroblasts or embryonic red cor puscles in the bone-marrow. In the anaemia secondary to malig nant disease, e.g., gastric cancer, the anaemia is due to a combina tion of several factors. First there is a toxaemic condition due to absorption of products of decomposition formed in the growth itself. But in addition there may be present loss of blood from haemorrhage ; an increase in the destruction of red corpuscles in some cases ; a disturbance of nutrition leading to a lack of proper food supply for the erythroblastic tissue ; and the possible action of the autolytic products of the cancer cells which may inhibit the activity of the bone-marrow. The evidence of in creased red corpuscle destruction can sometimes be obtained by examination of the spleen and liver, their cells containing a larger quantity of iron than normal, by examination of secretions or excretions, such as the bile and urine (haemoglobinuria), and by determining the fragility of the red corpuscles. The fragility of the red corpuscles is ascertained by determining their ability to withstand a hypotonic solution of sodium chloride without dis integrating, normal red corpuscles being able to resist a o.4% solution, whereas "fragile corpuscles" will discharge their haemo globin in a o.5% solution. The evidence of disturbance of the red bone-marrow is obtained by detailed examination of the blood, the cellular constituents being markedly altered. In the chronic anaemias regeneration and destruction, or loss, occur simulta neously, so that the blood picture gives an idea more of the capacity of the erythroblastic tissue to respond than of the amount of destruction that is occurring. In aplastic anaemia, a rare condition, the red bone-marrow, does not respond, and as a result the anaemia runs a rapid and progressive course without remissions, contrary to the usual course of the chronic anaemias.

Chlorosis.

Chlorosis and pernicious anaemia are primary anaemias that deserve special discussion because of their common occurrence. Chlorosis occurs almost exclusively in females be tween the ages of 14 and 25, the most frequent ages of onset being 14 and 15. This disease is characterized by a pronounced haemoglobin deficiency without a proportional decrease in red corpuscles. It is rarely directly fatal and is fortunately very amen able to treatment with iron preparations, blood transfusions being required only in advanced and stubborn cases. The administra tion by mouth of bone-marrow and spleen is also beneficial. Re currences of the disease are quite common. The cause of chlorosis is unknown. All evidence shows that a haemolytic agent is prob ably not responsible. The erythroblastic tissue is at fault, particu larly in the formation of haemoglobin. The fact that iron is so beneficial suggests that iron starvation is in some way related to the primary cause, which is also related in some way to the age of puberty and the function of menstruation. Because of this latter factor, some believe that the glands of internal secretion, especially the ovary, are at fault ; but no conclusive evidence is as yet available. An improper diet, overwork, worry and lack of fresh air are predisposing factors. Chlorosis does not occur fre quently in country-bred girls, which is probably due to the greater exposure to sunshine and "outdoor life," which these girls enjoy. In towns, too, it is less common than formerly. The symptoms of chlorosis are in general those of anaemia.

Pernicious Anaemia.

Pernicious anaemia is a disease of middle life and is twice as common in males as in females. It is characterized by a progressive anaemia interrupted by periods of temporary improvement, and by a fatal termination almost without exception in from two to five years, the body being rarely emaciated. The onset of this disease is slow and insidious. The skin is pale and later takes on a lemon tint. Languor, weakness and breathlessness are not marked at first, but later become ex treme. The heart palpitates readily. The mucous membrane of the mouth is glossy and appears bloodless ; the tongue is sore. The appetite fails and quite early in the disease acid disappears from the gastric secretion. Attacks of diarrhoea and abdominal pain frequently occur. There is a tendency to bleed into the skin and serous surfaces. Some patients experience sensations of numbness and tingling and complain of neurotic pains.

The blood picture is much changed, the red corpuscles being greatly reduced in number and very abnormal in shape and size, as well as in other respects. The red corpuscles contain an abun dance of haemoglobin, the colour index being greater than 1.o. The white blood corpuscles are generally normal or diminished in number, but frequently abnormal forms are present. On post mortem examination the bone-marrow is red and hyperplastic, except in cases of aplastic anaemia ; lesions of the spinal cord are found ; the gastric mucosa is frequently atrophic ; the internal organs show fatty degeneration ; the lymph glands may be deep ened in colour (haemolymph glands), and there is much iron pigment in the kidneys, liver and spleen.

In contrast to chlorosis, there appears to be no serious difficulty in the formation of haemoglobin in pernicious anaemia. Many evidences of excessive blood destruction are present, particularly the increased iron content of the organs, free haemoglobin in the blood serum and urine, the frequent occurrence of jaundice, and the increased fragility of the red corpuscles. A condition simulat ing pernicious anaemia occurs in continued poisoning with tol nylendiamine and ricin and in patients infected with bothrioce phalus, an intestinal parasite that produces a haemolytic agent.

Haemolytic substances are said to be present in the intestine of anaemic patients that have chronic intestinal disorders, and recently a condition similar to pernicious anaemia has been observed to occur following intestinal stasis. B. aerogenes capsula tus, which frequently inhabits the intestine of man, produces a haemolytic agent, and it is reported that they occur in increased numbers in the intestines of patients that have pernicious anaemia and that their number decreases during the remissions. The feed ing of these bacteria in large numbers, or the intravenous injec tion of their products, produces in animals a condition quite like pernicious anaemia in man. Buckman and Horrall report that an haemolytic substance is present in the serum of pernicious anae mia patients.

Some observers believe that the stomach is in some way related to the cause, because of the high incidence of absence of acid in the stomach (achlorhydria) of patients suffering with this disease and because this disease sometimes occurs after total removal of the stomach. The absence of the acid in the stomach is said to favour the growth of bacteria that produce haemolytic poisons. After total gastrectomy in dogs a grave anaemia is found, which, however, has been controlled by the administration of iron and cod-liver oil. Although the more recent evidence seems to show that the change in the stomach is primary, it is commonly held to be secondary, as are the changes in the bone-marrow and nervous system, to the action of a toxin, irrespective of its source.

(A. C. I.) Treatment and Diet.—As regards treatment, Minot and Murphy of the Harvard Medical School showed in 1926 that very much may be done to stimulate blood-production and improve the patient's condition by feeding with liver. About half a_ pound of liver must be taken daily until the normal blood picture is restored which may be in a few weeks ; subsequently the amount of liver may be reduced. In 1927 Cohn, Minot, Murphy and others found that a non-protein extract from liver containing the unknown factor could be used with equal success. These results have been confirmed in Great Britain, and in March 1928 the Medi cal Research Council, in a preliminary report, stated that extracts prepared by certain commercial drug firms had proved satisfac tory. Certain other animal organs, as well as apricots, peaches and plums, are also of service. It has been debated whether iron must be in organic combination to be utilizable in blood regeneration or whether a simple inorganic salt (as ferrous carbonate) will suf fice, but the evidence is that the form and quantity are not signifi cant. Beef kidney and raspberries contain much more iron than do beef liver, apricots and peaches, but are much less effective in blood regeneration. Some unknown substance is supplied by the effective foods enabling the body to utilize the iron. Apricots, peaches and prunes are about as effective as bone marrow, pan creas and spleen; raisins and grapes rank lower, about on a par with brain tissue. The dried fruits are as effective as the fresh and in this connection are far superior to dairy products.

At the same time it may be noted that while diet may help, the liver treatment apparently affects the formation of blood alone and not the underlying condition on which the pernicious anaemia depends ; the achlorhydria in particular is unaffected. Hence gen eral measures must be undertaken besides the liver treatment. The source of the toxaemia should be looked for. Plenty of fresh air, sunlight and cod-liver oil are indicated. Dilute hydrochloric acid by mouth improves digestion. Removal of the spleen has been tried extensively, but without definite benefit. It is of great benefit, however, in splenic anaemia. Repeated blood transfusion is sometimes of great, though temporary value.

The benefits of liver diet for pernicious anaemia have been successfully demonstrated, both in America and Great Britain. The treatment was first suggested by G. R. Minot and W. P. Murphy of Harvard Medical school. Because a daily liver diet is intolerable to most patients, there have been extensive efforts to isolate the active principle in liver. As a result, liver extracts from the United States, Germany and Great Britain are now on the market. Since the extracts are soluble in water, a single dose, equivalent to nearly 3o oz. of whole liver, can be given a patient unable to take solid food. It has been demonstrated also that anaemics may obtain variety in apricots, peaches and prunes, either fresh or dried, and in certain other animal organs, such as brain tissue, bone-marrow, pancreas and spleen.

Other Forms of Anaemia.—There are other diseases of the blood and blood-forming organs, such as lymphosarcoma, Hodg kin's disease, chloroma, leucaemia and anaemia pseudoleucaemia of children, in which anaemia occurs. In these diseases the dis turbance chiefly involves the white corpuscles, or leucocytes, and hence these diseases are not 'to be considered in a general discus sion of anaemia. (X.) BIBLIOGRAPHY.-F. B. Mallory and J. H. Wright, Pathological Bibliography.-F. B. Mallory and J. H. Wright, Pathological Technique (1918) ; Anders, Am. Jour. Med. Sci., vol. 158, p. 659 (1919) ; F. Tice, Practice of Medicine, vol. 6 (1921) ; A. F. Hurst, Guy's Ilosp. Rep., vol. 73 (1923), and Lancet (Jan. and June 1923) ; Faber and Gram, Arch. Int. Med., vol. 34, P. 827 (1924) ; Ivy and Farrell, Proc. Am. Physiol. Soc. (Dec. 1925) ; Kahn and Torrey, Jour. Inf. Dis., vol. 37, p. 161 (1925) ; G. R. Minot and W. P. Murphy, Jn. Amer. Med. Assn., 1926, 87, 470; H. F. Brewer, A. Q. Wells, and F. R. Fraser, Brit. Med. Jo., 1927, i., 165 (biblogr.) ; Medical Research Council, Brit. Med. Jn., 1927, i.,