which is produced by certain organic and inorganic poisons; it is seen especially in phosphorus and chloroform poisoning. The changes are also common in pernicious anaemia, advanced chlorosis, cachexias, and in the later stages of starvation. In diabetes mellitus, in which there is marked derangement in metabolism, extreme fatty changes are occasionally found in the organs, and the blood may be loaded with fat globules. This lipoemic condition may cause embolism, the plugging especially occurring in the lung capillaries.
Fatty degeneration is common to all dead or decaying tissues in the body, and may be followed by calcification.
Autolysis is a disintegration of dead tissues brought about by the action of their own ferments, while degeneration takes place in the still living cell. The study of autolytic phenomena which closely simulates the changes seen in the degenerating cell has thrown much light on these degenerative processes.
These conditions may be purely physiological, e.g. in the mammary gland during lactation or in sebaceous glands, caused by increased functional activity. It may follow a diminished functional activity, as in the atrophying thymus gland and in the muscle cells of the uterus after parturition.
Any of the abnormal conditions that bring about general or local defective nutrition is an important factor in producing fatty degeneration.
The part played by fats and closely allied compounds in normal and abnormal metabolism need not here be discussed, as the subject is too complex and the views on it are conflicting. It will be sufficient to state briefly what appears to be the result of recent investigation.
The neutral fats are composed of fatty acids and glycerin. In the physiological process of intestinal digestion, the precursors of such fats are split up into these two radicles. The free fatty acid radicle then unites with an alkali, and becomes transformed into a soluble soap which is then readily absorbed in this fluid condition by the epithelial cells of the mucous membrane. There it is acted on by ferments (lipases) and converted into neutral fat, which may remain in the cell as such. By the reverse action on the part of the same ferments in the cell, these neutral fats may be redissolved and pass into the lacteals.
Many cells throughout the body contain this ferment. The soluble soaps which are probably conveyed by the blood will be quickly taken up by such cells, synthetized into neutral fats, and stored in a non-diffusible form till required. The fat in this condition is readily recognized by the usual microchemical and staining reactions. As fat is a food element essential to the carrying out of the vital energies of the cell, a certain amount of fatty matter must be present, in a form, however, unrecognizable by our present microchemical and staining methods.
Some investigators hold that the soaps may become combined with albumin, and that on becoming incorporated with the cytoplasm they can no longer be distinguished as fat. If from some cause the cell be damaged in such a way as to produce disintegration of the cytoplasm, there will be a breaking down of that combination, so that the fat will be set free from the complex protein molecule in which it was combined as a soap-albumin, and will become demonstrable by the usual methods as small droplets of oil. This splitting up of the fats previously combined with albumin in the cell by the action of natural ferments—lipases—and the setting free of the fats under the influence of toxins represent the normal and the pathological process in the production of so-called fatty degeneration.
Calcification.—Calcification and calcareous deposits are extremely common in many pathological conditions.
There are few of the connective tissues of the body which may not become affected with deposits of calcareous salts (fig. 47, Pl. V.). This condition is not so frequently seen in the more highly differentiated cells, but may follow necrosis of secreting cells, as is found in the kidney, in corrosive sublimate poisoning and in chronic nephritis. These conditions are quite distinct from the normal process of ossification as is seen in bone.
Many theories have been advanced to explain these processes, and recently the subject has received considerable attention. The old idea of the circulating blood being supersaturated with lime salts which in some way had first become liberated from atrophying bones, and then deposited, to form calcified areas in different tissues will have to be given up, as there is no evidence that this “metastatic” calcification ever takes place. In all probability no excess of soluble lime salts in the blood or lymph can ever be deposited in healthy living tissues.
At the present day both experimental and histological investigations seem to indicate that in the process of calcification there is a combination of the organic substances present in degenerated tissues, or in tissues of low vitality, with the lime salts of the body. From whatever cause the tissues become disorganized and undergo fatty degeneration, the fatty acids may become liberated and combine with the alkalies to form potash and soda soaps.
The potash and soda is then gradually replaced by calcium to form an insoluble calcium soap. The interaction between the soaps, the phosphates and the carbonates which are brought by the blood and lymph to the part results in the weaker fatty acids being replaced by phosphoric and carbonic acid, and thus in the formation of highly insoluble calcium phosphate and carbonate deposits in the disorganized tissues.
Pathological Pigmentations.—These pigmentary changes found in abnormal conditions are usually classified under (1) Albuminoid, (2) Haematogenous, (3) Extraneous.
1. The normal animal pigments and closely allied pigments are usually found in the skin, hair, eye, supra-renal glands, and in certain nerve cells. These represent the albuminoid series, and are probably elaborated by the cells from albuminous substances through the influence of specific ferments. This pigment is usually intracellular, but may be found lying free in the intercellular substance, and is generally in the form of fine granules of a yellowish-brown or brown-black colour. In the condition known as albinism there is a congenital deficiency or entire absence of pigment. Trophic and nervous conditions sometimes cause localized deficiency of pigment which produces white areas in the skin.
Excessive pigmentation of tissue cells (fig. 48, Pl. V.) is seen in old age, and usually in an accompaniment of certain atrophic processes and functional disorders. Certain degenerative changes in the supra-renal glands may lead to Addison’s disease, which is characterized by an excessive pigmentary condition of the skin and mucous membranes. This melanin pigment is found in certain tumour growths, pigmented moles of the skin, and especially in melanatic sarcomata (fig. 49, Pl. V.) and cancer. The action of the sun’s rays stimulates the cells of the skin to increase the pigment as a protection to the underlying tissues, e.g. summer bronzing, “freckles,” and the skin of the negro.
The coloured fats, or lipochromes, are found normally in some of the cells of the internal organs, and under certain pathological conditions. This pigment is of a light yellow colour, and contains a fatty substance that reacts to the fat-staining reagents. Little is known regarding this class of pigment.
2. Haematogenous pigments are derived from the haemoglobin of the red blood corpuscles. These corpuscles may break down in the blood vessels, and their colouring material (haemoglobin) is set free in the serum. But their disintegration is more commonly brought about by “phagocytosis” on the part of the phagocytic cells in the different organs concerned with the function of haemolysis, i.e. the liver, spleen, haemolymph glands and other tissues.
The haemoglobin may be transformed into haematoidin, a pigment that does not contain iron, or into a pigment which does contain iron, haemosiderin.
The haematoidin pigment may vary in colour from yellowish or orange-red to a ruby-red, and forms granular masses, rhombic prisms or acicular crystals. It can be formed independently of cell activity, nor does it require oxygen. These crystals are extremely resistant to absorption, are found in old blood clots, and have been known to persist in old cerebral haemorrhages after many years. Haematoidin in normal metabolism is largely excreted by the liver in the form of bilirubin.
Haemosiderin, an iron-containing pigment (probably an hydrated ferrous oxide), is found in more or less loose combination with protein substances in an amorphous form as brownish or black granules. Cellular activity and oxygen appear to be essential for its development; it is found usually in the cells of certain organs, or it may be deposited in the intercellular tissues. Haemosiderin in the normal process of haemolysis is stored up in the cells of certain organs until required by the organism for the formation of fresh haemoglobin. In diseases where haemolysis is extreme, particularly in pernicious anaemia, there are relatively large quantities occasionally as much as ten times the normal amount of haemosiderin deposited in the liver.
In hepatogenous pigmentation (icterus or jaundice) we have the iron-free pigment modified and transformed by the action of the liver cells into bile pigment (bilirubin). If the discharge of this
