malarial mill anaemia. By Patrick IIehir, m.d., f.r.s.e., d.p.h. ((Iamb.), Lecturer on Medicine and Pathology, Hyderabad Medical School. '
(Continued from page 248.) Felkin Dr. (Edinburgh) recently read a paper on Malaria and Enteric Fever in Central Africa Black- water" and (including the so-called typho-malarial fevers) and on the possible antagonism between malaria and phthisis, and in that lie laid special emphasis upon the importance of the existence of pigment free and in cells other than the red-blood corpuscles in the blood. Several urinary pigments other than normal colouring matters of the urine have been observed during malarial fevers. Particles of such pigment are at times to he found in the urine, all of them resulting from the decomposition f certain of the normal colouring matter of the blood. Brown or inky black pigments sometimes appear in the urine of patients suffering from melanotic cancer. When recently voided such urine is generally still free of any brownish discoloration; this is developed only after the urine has been in contact with the air for some time, or on adding to it oxidising substances, such as chlorate of potash, chromic acid, nitric acid, &c. It is not }Tet certain whether this brown or black colouring matter is really of pathological origin or is merely one of the normal urinary pigments present in unduly great quantity; it is most probably the former. It differs from the other familiar colouring substances found in the urine in offering greater resistance to their usual solvents, and it also differs from the pigments met with in malarial infection. There is still another brown pigment sometimes discovered in the urine, and due to the presence of catechin; it is formed only after the urine has stood for a considerable period in contact with the air or when decomposition is beginning, and lias hitherto been observed in only a few cases in the human subject (Muller and Epstein). A urine containing this substance becomes intensely green on adding to it one drop of chloride of iron, and this colour changes to violet on the further addition of ammonia or the bicarbonate of soda. The malarial urinary pigments are not to be confounded with this. The manner of making the distinction 1 hope to make the subject of a future communication. Amongst the accompaniments of a^ue the most frequent are enlargement and induration of the spleen, liver, &c.; these, although secondary phenomena, do not form an essential part, of the poisoning. But there is one constant phenomenon in all cases of malarial poisoning and that is malarial melansemia. This is no mere accidental occurrence; it is invariable. It is probable that a large amount of the pigment deposited in the tissues and organs comes from the spleen, not as the result of the disin"
64
454
INDIAN MEDICAL GAZETTE.
tegration of hemoglobin from the death of redblood corpuscles as was formerly supposed, but
because this organ is the chief temporary abode or resting-place of the malarial organism during the non-pyrexial periods of malarial poisoning. This pigmentary deposit takes place specially in the spleen and liver, but particularly in the former. The spleen is seen to be of a peculiar dark-brown or blackish colour, and often of a slaty hue, due to the infiltration of the colouring matter throughout its structure. Larger quantities are always to be found in the blood vessels leading from the spleen, and in all the organs connected with the splenic blood through the portal vein. The pigment is, as a rule, excessively black and granular. We have in two cases abstracted blood from the spleen in cases of malarial hypertrophy of that organ with adhesion to the abdominal wall, and in both the amount of pigment in the field of each slide was extraordinary, whilst the misshapen red-blood corpuscles and the leucocytes and phagocytes filled with pigmentary particles, gave the whole field a very curious appearance indeed. The pigmentary change in the liver is of a like kind, and although the colour is not so characteristic yet the capsule of Glisson, the interlobular connective tissue, and even the parenchyma, are the seats of deposit of this pigment. Occasionally masses of pigment are also seen beneath the capsule. One reminder might here be inserted, that the peculiar slate-grey discoloration sometimes seen post-mortem on the solid abdominal viscera as a result of the action of H2 S, which is generated from decomposition processes of the iron contained in the haemoglobin of the blood, should be distinguished from the condition under consideration. But those who have performed even a few post-mortems carefully are not likely to make this error. The red marrow of bones is likewise one of the seats of election not only for the "resting" Plasmodium malarire, but it is also one of those places to which malarial pigment is conveyed in considerable quantities. It is quite possible that the pains in the limbs, joints, and bones general" ly, often colloquially termed boneachishness," may be accounted for by these two phenomena. The alteration which occurs from the breaking up of the red-blood corpuscles gives rise to the accumulation of pigment which is thus formed, and it is probable that the pigment is produced by the plasmodium malariee. That the redblood corpuscles are the origin of the pigment, all facts, especially the spectroscopic characters of the pigment, go to prove. We cannot push this theory of the parasitic effect on the red-blood cells as the cause of the production of the pigment too far, however, and for the present at least, we must confess that as
[Dec.
1894.
as the splenic pigment is concerned, we have positive proof that it is created by the parasitic growth in red-blood corpuscles, especial^ as* Laveran's views are still sub judice.
far no
-
^
The presence of this form of pigment is specially connected with the decrease of malarial poisoning and with malarial fevers, and it is then typically met with in the pigmented spleen.'" The pigment particles are conveyed from the?spleen to the liver, brain and internal organs,"""" and may thus give rise to deterioration of structure and of function of the affected organs. Danielewsky has described in the red-blood corpuscles of birds, fishes and tortoises, peculiar parasitic organisms which in their evolution from pseudo-vacuoles from which the parasites are subsequently set free, and in this process deposit granular pigment free in the blood. In this state the spleen corpuscles also convey large quantities of pigment to the liver, and pigment particles have actually been seen in the hepatic capillaries; eventually the pigment is found at the more distant parts of the circulation and becomes fixed in the interstitial tissue of various organs of the body. It is common for one clinical manifestation of malarial poisoning to change to another^" This is seen in malarial diarrhoea alternating with ague. Such interchanges are more often met with in children than adults in the Deccan of India. Conversely a malarial fever may disand be replaced by, or but leave behind appear, it such conditions as neuralgia, malarial rheumatism, etc. The absence of black pigmentary matter from the blood in all fevers, except those of malarial origin, gives melansemia another important aspect ; its presence in malarial fevers, mild and severe, makes it absolutely diagnostic. Indeed, just as the comma-bacillus, apart from any etiological considerations, is considered pathognomonic of cholera, so may the melansemia be considered characteristic of malarial fevers. No one denies the presence of the pigment in malarial fevers, although we think it has not been accorded that amount of attention which should attach to so important a fact from a pathological and clinical point of view, nor do any authorities discredit the red-blood corpuscles as the origin of the pigment; but there is still considerable difference of opinion as to the manner in which the disintegration of hemoglobin takes place and the pigment is set free. Where there is sufficient pigment in the body to give rise to its external deposition in mucous membranes and skin, it may, as a rule, be'taken for granted that most of the internal organs are charged to overflowing with the material; at least this I have found to be the case in all the post-mortem examinations one has had the opportunity of making in these cases, especially the liver and the spleen.
Dec.
1894.]
A CASE OF DEATH UNDER CHLOROFORM.
is often diseases, which do not appear to be connected with malaria but its presence indicates that the clnet factor in the patient's ailment is malaria, ancl that the chief remedy is quinine. Larger quantities are always to be found m the blood-vessels, the spleen and the parts connected with the splenic blood through the portal vein. This pigment is, as a rule, excessively black and granular. Most pathologists believe that the pigment itself is the resulting product in the final stage of a series of disintegrations which are brought about by the malarial parasite. So that the very presence of the pigment may be taken as a sign of the presence of the parasite or of its recent
Indeed, pigment in large quantities unexpectedly met with in pyrexia!
most ?
-
.
#
existence
?
There is still doubt as to the exact chemical nature of the pigment. It is known to contain iron and likewise carbon, hydrogen and oxygen. This is not surprising when we consider that Laveran's views are not as yet accepted. In a matter requiring such close observation as the origin and development of these micro-organisms and their relations to different forms of malarial fevers, there are many possibilities of error occurring when we take into consideration another factor the possibility of there being more than This renders obvious one variety of the parasite. of opinion should arise amongst differences why observers. Records of cultivations and reproductions oi the parasite have hitherto failed, although some of the greatest bacteriologists and pathologists have been endeavouring to work out this eviclence. The mechanism of the process of bronzing of the skin in Addison's disease has never yet been satisfactorily described_ any better than has it been shown why the pigment of melaneemia of
melanotic sarcomata or cancer does not give any of the spectroscopic signs of the blood pigments. In acute general tuberculosis melansemia is also met with, but not invariably, and not throughout the period of the disease or in the same quantity, or with constance in the same case, whereas in malaria it is always piesent. Of the nervous diseases due to evident structural lesions, apoplexy followed by hemiplegia is the most frequent malady met with in Hyderabad and its suburbs, and as it occurs in comparatively young people without heartdisease or syphilis, one is driven to the conclusion that it often arises from the blocking up of the cerebral arteries by emboli of pigment and
frequently
malarial parasitic organisms. The fact that the arteries of basal ganglia and general substance of the cerebrum are terminal arteries lends support to this view, as does also their great comparative amenability to treatment or even to
spontaneous disappearance
of the
symptoms.
455
There are many animal organisms which in their growth produce pigments or colouring matters, having a close resemblance or rather analogy to many of the lower forms of vegetable life. The widespread distribution of bacilli in nature has led to the inference that this pigment-producing faculty is a most important factor. The varieties of colouring matter produced has led to different names being given to microbes of this kind; as the bacillus cyaneus, bacillus pyogenes albus, auriens, &c. We believe that the blood-vessels, at least the are all more or less diseased in the chronic forms of malarial poisoning. That they are so in the radicles of the splenic artery, splenic vein, arterioles of the kidney, liver, including portal vein and hepatic artery radicles, and those of the brain we have no doubt; for we have examined all these after various postmortems and found them to be so.
arterioles,
(To
be
continued.)
(Continued from page 248.) Felkin Dr. (Edinburgh) recently read a paper on Malaria and Enteric Fever in Central Africa Black- water" and (including the so-called typho-malarial fevers) and on the possible antagonism between malaria and phthisis, and in that lie laid special emphasis upon the importance of the existence of pigment free and in cells other than the red-blood corpuscles in the blood. Several urinary pigments other than normal colouring matters of the urine have been observed during malarial fevers. Particles of such pigment are at times to he found in the urine, all of them resulting from the decomposition f certain of the normal colouring matter of the blood. Brown or inky black pigments sometimes appear in the urine of patients suffering from melanotic cancer. When recently voided such urine is generally still free of any brownish discoloration; this is developed only after the urine has been in contact with the air for some time, or on adding to it oxidising substances, such as chlorate of potash, chromic acid, nitric acid, &c. It is not }Tet certain whether this brown or black colouring matter is really of pathological origin or is merely one of the normal urinary pigments present in unduly great quantity; it is most probably the former. It differs from the other familiar colouring substances found in the urine in offering greater resistance to their usual solvents, and it also differs from the pigments met with in malarial infection. There is still another brown pigment sometimes discovered in the urine, and due to the presence of catechin; it is formed only after the urine has stood for a considerable period in contact with the air or when decomposition is beginning, and lias hitherto been observed in only a few cases in the human subject (Muller and Epstein). A urine containing this substance becomes intensely green on adding to it one drop of chloride of iron, and this colour changes to violet on the further addition of ammonia or the bicarbonate of soda. The malarial urinary pigments are not to be confounded with this. The manner of making the distinction 1 hope to make the subject of a future communication. Amongst the accompaniments of a^ue the most frequent are enlargement and induration of the spleen, liver, &c.; these, although secondary phenomena, do not form an essential part, of the poisoning. But there is one constant phenomenon in all cases of malarial poisoning and that is malarial melansemia. This is no mere accidental occurrence; it is invariable. It is probable that a large amount of the pigment deposited in the tissues and organs comes from the spleen, not as the result of the disin"
64
454
INDIAN MEDICAL GAZETTE.
tegration of hemoglobin from the death of redblood corpuscles as was formerly supposed, but
because this organ is the chief temporary abode or resting-place of the malarial organism during the non-pyrexial periods of malarial poisoning. This pigmentary deposit takes place specially in the spleen and liver, but particularly in the former. The spleen is seen to be of a peculiar dark-brown or blackish colour, and often of a slaty hue, due to the infiltration of the colouring matter throughout its structure. Larger quantities are always to be found in the blood vessels leading from the spleen, and in all the organs connected with the splenic blood through the portal vein. The pigment is, as a rule, excessively black and granular. We have in two cases abstracted blood from the spleen in cases of malarial hypertrophy of that organ with adhesion to the abdominal wall, and in both the amount of pigment in the field of each slide was extraordinary, whilst the misshapen red-blood corpuscles and the leucocytes and phagocytes filled with pigmentary particles, gave the whole field a very curious appearance indeed. The pigmentary change in the liver is of a like kind, and although the colour is not so characteristic yet the capsule of Glisson, the interlobular connective tissue, and even the parenchyma, are the seats of deposit of this pigment. Occasionally masses of pigment are also seen beneath the capsule. One reminder might here be inserted, that the peculiar slate-grey discoloration sometimes seen post-mortem on the solid abdominal viscera as a result of the action of H2 S, which is generated from decomposition processes of the iron contained in the haemoglobin of the blood, should be distinguished from the condition under consideration. But those who have performed even a few post-mortems carefully are not likely to make this error. The red marrow of bones is likewise one of the seats of election not only for the "resting" Plasmodium malarire, but it is also one of those places to which malarial pigment is conveyed in considerable quantities. It is quite possible that the pains in the limbs, joints, and bones general" ly, often colloquially termed boneachishness," may be accounted for by these two phenomena. The alteration which occurs from the breaking up of the red-blood corpuscles gives rise to the accumulation of pigment which is thus formed, and it is probable that the pigment is produced by the plasmodium malariee. That the redblood corpuscles are the origin of the pigment, all facts, especially the spectroscopic characters of the pigment, go to prove. We cannot push this theory of the parasitic effect on the red-blood cells as the cause of the production of the pigment too far, however, and for the present at least, we must confess that as
[Dec.
1894.
as the splenic pigment is concerned, we have positive proof that it is created by the parasitic growth in red-blood corpuscles, especial^ as* Laveran's views are still sub judice.
far no
-
^
The presence of this form of pigment is specially connected with the decrease of malarial poisoning and with malarial fevers, and it is then typically met with in the pigmented spleen.'" The pigment particles are conveyed from the?spleen to the liver, brain and internal organs,"""" and may thus give rise to deterioration of structure and of function of the affected organs. Danielewsky has described in the red-blood corpuscles of birds, fishes and tortoises, peculiar parasitic organisms which in their evolution from pseudo-vacuoles from which the parasites are subsequently set free, and in this process deposit granular pigment free in the blood. In this state the spleen corpuscles also convey large quantities of pigment to the liver, and pigment particles have actually been seen in the hepatic capillaries; eventually the pigment is found at the more distant parts of the circulation and becomes fixed in the interstitial tissue of various organs of the body. It is common for one clinical manifestation of malarial poisoning to change to another^" This is seen in malarial diarrhoea alternating with ague. Such interchanges are more often met with in children than adults in the Deccan of India. Conversely a malarial fever may disand be replaced by, or but leave behind appear, it such conditions as neuralgia, malarial rheumatism, etc. The absence of black pigmentary matter from the blood in all fevers, except those of malarial origin, gives melansemia another important aspect ; its presence in malarial fevers, mild and severe, makes it absolutely diagnostic. Indeed, just as the comma-bacillus, apart from any etiological considerations, is considered pathognomonic of cholera, so may the melansemia be considered characteristic of malarial fevers. No one denies the presence of the pigment in malarial fevers, although we think it has not been accorded that amount of attention which should attach to so important a fact from a pathological and clinical point of view, nor do any authorities discredit the red-blood corpuscles as the origin of the pigment; but there is still considerable difference of opinion as to the manner in which the disintegration of hemoglobin takes place and the pigment is set free. Where there is sufficient pigment in the body to give rise to its external deposition in mucous membranes and skin, it may, as a rule, be'taken for granted that most of the internal organs are charged to overflowing with the material; at least this I have found to be the case in all the post-mortem examinations one has had the opportunity of making in these cases, especially the liver and the spleen.
Dec.
1894.]
A CASE OF DEATH UNDER CHLOROFORM.
is often diseases, which do not appear to be connected with malaria but its presence indicates that the clnet factor in the patient's ailment is malaria, ancl that the chief remedy is quinine. Larger quantities are always to be found m the blood-vessels, the spleen and the parts connected with the splenic blood through the portal vein. This pigment is, as a rule, excessively black and granular. Most pathologists believe that the pigment itself is the resulting product in the final stage of a series of disintegrations which are brought about by the malarial parasite. So that the very presence of the pigment may be taken as a sign of the presence of the parasite or of its recent
Indeed, pigment in large quantities unexpectedly met with in pyrexia!
most ?
-
.
#
existence
?
There is still doubt as to the exact chemical nature of the pigment. It is known to contain iron and likewise carbon, hydrogen and oxygen. This is not surprising when we consider that Laveran's views are not as yet accepted. In a matter requiring such close observation as the origin and development of these micro-organisms and their relations to different forms of malarial fevers, there are many possibilities of error occurring when we take into consideration another factor the possibility of there being more than This renders obvious one variety of the parasite. of opinion should arise amongst differences why observers. Records of cultivations and reproductions oi the parasite have hitherto failed, although some of the greatest bacteriologists and pathologists have been endeavouring to work out this eviclence. The mechanism of the process of bronzing of the skin in Addison's disease has never yet been satisfactorily described_ any better than has it been shown why the pigment of melaneemia of
melanotic sarcomata or cancer does not give any of the spectroscopic signs of the blood pigments. In acute general tuberculosis melansemia is also met with, but not invariably, and not throughout the period of the disease or in the same quantity, or with constance in the same case, whereas in malaria it is always piesent. Of the nervous diseases due to evident structural lesions, apoplexy followed by hemiplegia is the most frequent malady met with in Hyderabad and its suburbs, and as it occurs in comparatively young people without heartdisease or syphilis, one is driven to the conclusion that it often arises from the blocking up of the cerebral arteries by emboli of pigment and
frequently
malarial parasitic organisms. The fact that the arteries of basal ganglia and general substance of the cerebrum are terminal arteries lends support to this view, as does also their great comparative amenability to treatment or even to
spontaneous disappearance
of the
symptoms.
455
There are many animal organisms which in their growth produce pigments or colouring matters, having a close resemblance or rather analogy to many of the lower forms of vegetable life. The widespread distribution of bacilli in nature has led to the inference that this pigment-producing faculty is a most important factor. The varieties of colouring matter produced has led to different names being given to microbes of this kind; as the bacillus cyaneus, bacillus pyogenes albus, auriens, &c. We believe that the blood-vessels, at least the are all more or less diseased in the chronic forms of malarial poisoning. That they are so in the radicles of the splenic artery, splenic vein, arterioles of the kidney, liver, including portal vein and hepatic artery radicles, and those of the brain we have no doubt; for we have examined all these after various postmortems and found them to be so.
arterioles,
(To
be
continued.)
