DISTURBANCES OF PIGMENT METABOLISM: A Brief Review of Exogenous Pigmentation in Animals.

DISTURBANCES OF PIGMENT METABOLISM: A Brief Review of Exogenous Pigmentation in Animals.

Bhagwat P. N.*, Moregaonkar S.D.¹, Gangane G.R.², Rathod P.R.³, Swami S.B.⁴,

Patil A. A.⁵ and Jogdand B. M.⁶

Department of Veterinary Pathology

College of Veterinary and Animal Sciences, Parbhani – 431402 (MS)

Maharashtra Animal and Fishery Sciences University, Nagpur – 44000

WHAT IS A PIGMENT:

        “Various coloring agents found in the body are called as pigments”.

WHAT IS A PIGMENTATION:

1) Coloration in plants, animals, or man caused by the presence of pigments

2) The deposition of pigment in animals, plants, or man

CLASSIFICATION OG PIGMENTATION:

          These pigments are classified into two ways-

• Endogenous: Pigments formed within the body. Ex- Melanin, Bilirubin, etc.
• Exogenous: Pigments entered in the body from outside. Ex- Coal dust, Lead, etc.

1. EXOGENOUS PIGMENTATION:

• Definition: Foreign substances entering the body by way of respiratory and digestive tracts and the skin and subsequently deposited in the tissues constitute exogenous type of pigmentation.
• In veterinary pathology only exogenous pigmentation of the lungs is of any significance (Runnells, et al. 1957).

Pneumoconiosis:

• Definition: Dusts of various kinds like coal dust, iron dust, stone dust, asbestos dust, ash dust, lead dust, pollen grains may be inhaled by animals. These dusts beside imparting a colour, cause fibrosis of the lungs and the condition is called as “Pneumoconiosis”.
• It is not an infectious disease but it is condition resulting from inhalation of dusts (DWHC Website).
• Dusts of various kinds like coal dust, iron dust, stone dust, asbestos dust, ash dust, lead dust, pollen grains may be inhaled by animals.
• These dusts beside imparting a color, cause fibrosis of the lungs and the condition is called as “Pneumoconiosis”.
• It is most commonly seen in the lungs of animals that live in or around cities, roads or industrial zones, where there is a high level of particulate air pollution. Pneumoconiosis may be a normal finding in the lungs of fossorial animal species such as badgers and moles and also seen in animals that have been exposed to drought conditions when the ground is dry and dusty (DWHC Website).
• Pneumoconiosis is a class of ‘interstitial lung disease’, where inhalationof dusthas caused interstitial fibrosis.
• Pneumoconiosis is one of the most common occupational diseases in the world.
• It is usually an occupational lung disease, typically from years of dust exposure during work in mining; textile milling; ship building, ship repairing and ship breaking; sand blasting; industrial tasks; rock drilling (subways or building pilings); or agriculture.
• Pneumoconiosis may be classified as either fibrotic (involving focal nodular or diffuse fibrosis) or nonfibrotic (involving particle-laden macrophages, with minimal or no fibrosis. Silicosis, coal worker pneumoconiosis, asbestosis, berylliosis, and talcosis are examples of fibrotic pneumoconiosis. Siderosis, stannosis, and baritosis are nonfibrotic forms of the disease. Silicosis, coal worker pneumoconiosis, and asbestosis are the three most common types of pneumoconiosis, whereas berylliosis, siderosis, stannosis, and baritosis are relatively uncommon (Chong, et al. 2006).
• Conditions caused by deposition of dust of various kinds in the body is as below:
• Coal dust- Anthracosis
• Stone dust- Silicosis
• Iron dust- Siderosis
• Asbestos dust- Asbestosis
• Fine stone dust- Chalcosis
• Cotton dust/lint- Byssinosis
• Tin oxide – Stannosis
• Barium dust – Baritosis

(Vegad, 2007)

Pathogenesis (In general):

• The reaction of the lung to mineral dusts depends on many variables (size, shape, solubility, and reactivity of the particles). Particles of 1 to 5 μm in diameter are the most dangerous, because they get lodged at the bifurcation of the distal airways (Popper, 2016).

Sequelae:

• Depending on extent and severity, it may cause death within months or years, or it may never produce symptoms.

1. Anthracosis:

• Definition: It is condition in which there is accumulation of carbon particles in the lungs usually it is coal dust (Vegad, 2007).
• The term anthracosis was first used by Stratton in 1838 to describe the lungs of coal workers (Vakharia, et al. 1990).
• Anthracosis is black pigment discoloration of bronchi, which can cause bronchial destruction and deformity (anthracofibrosis). It is a benign bronchial finding (Mirsadraee, et al. 2005).
• Animals affected: All animal species are susceptible to anthracosis. But this condition is seen in horses, cattle, dogs and cats that lives in industrial areas where stool & coal dust pollute the air.
• Mens and the mules working in coal mines are markedly afflicted, so that the heavily blackned lung is called as “miners lung” (Smith, et al. 1972).
• The lungs and related lymph nodes are the “primary sites” for anthracosis (Dahme et al. 1982, and Thomson 1984).
• When anthracosis is associated with inhalation of silica, the condition is termed as anthracosilicosis (Vakharia, et al. 1990).

Etiology:

• The pigmentation caused by the deposition in the tissues of carbon in the form of coal dust, smoke, motor vehicle exhaust waste and graphite.

Pathogenesis:

• The carbon particles may be inhaled and then will pigment the lung and regional nodes. Carbon may be introduced through cutaneous abrasion, and when this occurs, local tattooing in the form of a bluish black pigment is observed under the skin. The cutaneous pigmentation is especially common in animals injured in coal mines, around coal tipples or industrial coal yards (Runnells, et al. 1965).
• Due to rupture of anthracotic thoracic lymph node into a pulmonary vessel, systemic dissemination of carbon particles takes place.
• The pattern of distribution within the organs also suggests hematogenous spread (Vakharia, et al. 1990).

Macroscopically:

• Lungs appears firm, greyish black with few light-coloured elevated patches of emphysema (Darzi, et al. 2003).
• Lungs shows greyish black, spotty to confluent areas of about 5mm or larger especially in the areas surrounding the bifurcation of the bronchioles.
• In anthracosis ventral portion of lobes being affected more than the dorsal (Smith, et al. 1972).
• On incising bronchi and bronchioles, it contains thick tenacious mucous having black tinge. The hilar and bronchial lymph nodes were also blackish with concentration of black colour in paracortex (Darzi, et al. 2003).
• Anthracite or carbon in the lymph nodes is accumulated in the phagocytic portion of the lymph node which is in the medulla of all animals except the pig. In most animals therefore, the periphery of the lymph node will be white while the central portion will be grey or black. The lymph node of pig will have a grey or black periphery while the centre will be white. (Runnells, et al. 1965).
• Affected lung have a ‘Black peppered’ appearance (Ganti Sastry, 2001)
• In the lungs, black carbon particles were generally seen in the peribronchiolar and perivascular interstitium (Ozcan, et al. 2001).
• In addition to the lung, anthracosis may involve lymphoreticular organs and liver (Mirsadraee, et al. 2005).
• Mucosal deposits, as noted by inspection of bronchial epithelium, have been described as small black specks called “coal macules” (Vakharia, et. al. 1990).
• In cutaneous tissue it appears as a pigmented line or plaque corresponding to the shape of the injury which introduced the pigment. The pigment is located in the dermis and subcutaneous tissue and is not located in the epithelium (Runnells, et al. 1965).

Microscopically:

• Black carbon particles were found on the “alveolar walls”, within cytoplasm of alveolar macrophages and also on bronchial, bronchiolar epithelium. Carbon particles were also present in interalveolar and interlobular septa which had got thickened. The lymph node follicles showed hyperplasia and contained carbon particles in “paracortical region” (Darzi, et al. 2003).
• Pigmentation was found in the lungs, mediastinal and bronchial lymph nodes (Dahme and et.al. 1982, Thomson 1984, Argani, et al. 1989, and Roth et.al. 1998).
• Lung edema and scattered inflammatory cells are present (Mirsadraee, et al. 2005).
• In addition to dense peribronchial fibrosis with anthracotic pigmentation, marked perivascular fibrosis and several foci of peribronchial and perivascular granunlomatous infiammation are seen (Chung, et al. 1998).
• Van Gieson staining revealed a low-level fibrotic response (Ozcan and Beytut, 2001).
• The principal findings are anthracotic pigmentation of bronchial mucosa and bronchial luminal stenosis at the inlet of lobar or segmental brochi (Kim et al. 2009).
• The bronchi of the right lung were more frequently affected than those of the left lung. Further the area of nodules, consolidation, and atelectasis were the most frequent findings (Chung, et al. 1998).

Significance and Result:

• Reasonable amount of the pigment do little harm and cause no symptoms, but it remains in the tissue throughout life and excessive amount may cause slight fibrosis and suspected of predisposing to pulmonary infection (Smith, et al. 1972).
• To differentiate carbon particles from other pigments, particularly melanin; bleaching methods, including concentrated sulphuric acid, hydrogen peroxide, potassium permanganate and Mayer’s chlorine etc. were applied to both the lymph nodes and lungs (Ozcan et al. 2001).
• Wang and coworkers (2003) concluded that adenocarcinoma developing in heavily anthracotic lungs readily progresses to an advanced stage or that adenocarcinoma with a less favorable prognosis tends to develop in severely anthracotic lungs.

1. Silicosis:

• Definition: Silicosis is caused by the inhalation of fine particles of crystalline silicon dioxide (silica). Quartz is the most common form of crystalline silica (Weil, et al. 1994).
• In this condition, stone dust is inhaled and is more common in man than animals. Persons working in iron gold & diamond mines, stone quarries, glazing and enamel industries are frequently affected (Ganti Sastry, 2001).
• Sources-

The principal sources of exposure to silica are free silica in mining, quarrying, and tunneling; stonecutting, polishing, and cleaning monumental masonry; sandblasting and glass manufacturing; and, in foundry work, pottery and porcelain manufacturing, brick lining, boiler scaling, and vitreous enameling (Kim, et al. 2001).

 Pathogenesis:

Macroscopically (In general):

• Pleura is thickened
• Small, well-circumscribed nodules that are usually 2–5 mm in diameter but range from 1 to 10 mm, mainly involving the upper and posterior lung zones
• Focal emphysema and
• In rare cases, silicoproteinosis can be caused by high-dose inhalation, especially if amorphous silica is inhaled (Researchgate website)

Types:

• The disease occurs in two clinical forms: 1) Acute silicosis, which manifests as alveolar silicoproteinosis; and 2) Classic silicosis, which manifests as chronic interstitial reticulonodular disease (Chong et al., 2006)

1) Acute Silicosis (Silico-proteinosis):

• Result in the filling of the airspace in the lung with proteinaceous material and proliferation of type II pneumocytes and profuse surfactant production.

Microscopically,

• Mucosal epithelium of the trachea and primary bronchi had prominent mucinous hyperplasia is evident (Evans, et al. 1988).
• Acute silicosis shows severe alveolitis and alveolar filling with a substance that tests positive at periodic acid–Schiff staining.
• Pulmonary artery is thickened.
• Fetalization of alveolar epithelium may be noticed.
• Bilateral consolidation in perihilar regions.
• Sometimes, a “crazy-paving appearance” (airspace filling and interlobular septal thickening) caused by the presence of oedematous or fibrous tissue (Chong et al. 2006).

2) Classic Silicosis:

Microscopically:

• Silicotic nodules are composed of mature collagen in the central portion, with a peripheral zone of particle-laden macrophages that appears markedly different from the surrounding lung parenchyma. In color, the nodules range from slate grey to dense black, depending on the mineral contents in the silica (Fourth International Pneumoconiosis Conference, 1971).

1. A) Simple Form:

• Nodules are distributed throughout both lungs, but they tend to be predominantly located in the upper lobe and posterior portion of the lung. Calcification of nodules is seen. Hilar and mediastinal lymph node enlargement may precede the appearance of parenchymal nodular lesions. Calcification of lymph nodes is common and typically occurs at the periphery of the node. The so-called eggshell calcification pattern is highly suggestive of silicosis (Fourth International Pneumoconiosis Conference, 1971).

1. B) Complicated form or progressive massive fibrosis:

• Develops through the expansion and confluence of individual silicotic nodules.
• In silicosis, lightly pigmented nodules with smooth borders and a central area of whorled, acellular fibrosis in present. Fibrotic lesions usually appear in the upper zones of the lungs. They are known as “onion skin lesions” due to their characteristic concentrically arranged fibers of collagen (Delight, et al. 2022).
• At histopathologic analysis, a large conglomerate lesion, composed of multiple foci of central hyalinized collagen and a surrounding pigmented rim of macrophages, is observed. Focal necrosis is common in the central portions of the lesion and is occasionally associated with granulomatous inflammation (as in tuberculous infection) (Fourth International Pneumoconiosis Conference, 1971).

Significance and Result:

• Silica is powerful and insoluble irritant, cause extensive fibrosis which predisposes the lungs to tuberculosis.
• Carcinoma and tuberculosis are potential serious complications of silicosis (Fraser, et al. 1999)
• The disease is frequently associated with tuberculosis.
• It has been suggested by Fallon (1937) that the similarity of tuberculous and silicotic nodules is due to the fact that both are caused by the action of lipoids from damaged endothelial cells (Ough, 1949).

III. Siderosis:

• Definition: Siderosis is caused by the accumulation of iron oxide in macrophages within the lung due to inhalation of iron dust (Chong et al. 2006).
• Iron dust is inhaled chiefly as hematite or iron oxide from mines (Smith et al. 1972)

Sources:

• Pulmonary siderosis results from the inhalation of iron dust from mines, smelters, foundaries, or machine shops.
• It occurs in horses, mules and dogs, working in and around iron mines and foundries.
• Most cases of siderosis are seen in electric-arc and oxyacetylene welders, who may inhale finely divided particles of iron oxide (Kim et al. 2001).
• Cutaneous siderosis is observed in animals injured in areas, where iron dust is present the dust is carried into the cutaneous wounds and remains there after the wound have healed (Runnelle, et al. 1965).
• Siderosis of various organs occurs when iron compounds are injected into animals in the control of anaemia (Runnelle, et al. 1965).
• Inhaled iron with silica results in ‘Silicosiderosis (mixed-dust pneumoconiosis)’, can lead to appreciable pulmonary fibrosis and impairment to the exchange of gases in the lung and causes chronic general passive hyperaemia (Fraser et al. 1999).
• Silicosiderosis is seen in individuals involved in the mining and processing of iron ores, workers in iron and steel rolling mills, and foundry workers (Lucía Flors et al. 2009).

 Macroscopically:

• Iron just causes a brown or rusty red pigmentation of lungs.
• Pigmentation becomes diffuse as more and more dust enters in lungs.
• Emphysema is often seen and also airspace consolidation, predominantly in the lower lung zones (Chong et al. 2006).
• Due to mild irritating properly of iron, it causes slight fibrosis.
• If silicon is present in dust, extensive fibrosis of lungs occurs.

  Microscopically:

• Hematite and iron oxide appear as red crystals of varying size. They are anisotropic, appearing orange with polarized light and iron can be specifically demonstrated by “Prussian blue reaction” (Smith et al. 1972)
• Widespread areas of small centrilobular nodules and, less commonly patchy areas of ground-glass opacities without zonal predominance is also present (Lucía Flors, et al. 2009).
• The micronodules correspond to dust macules, which are collections of dust-laden macrophages aggregated along the perivascular and peribronchial lymphatic vessels (Chong, et al. 2006)
• Macrophages get accumulated in the alveolar space.

Test of siderosis:

• If tissue containing iron placed in potassium ferrocyanide solution and hydrochloric acid, tissue becomes blue in colour (Vegad, 2007).

Sequalae:

• Iron is only slightly soluble in the tissue fluids; it persists in the tissues for life of the individual.
• The mineral does not incite fibrosis or an inflammatory reaction and therefore of little significance (Runnelle, et al. 1965).
• Siderosis is not usually associated with fibrosis or functional impairment (Lucía Flors, et al. 2009).

1. Asbestosis

• Definition: Asbestosis is a chronic (long term) lung condition caused by prolonged inhalation of asbestos (Vegad, 2007).

Causes:

• The type, size, and durability of asbestos fibers may be important in toxicity and pathogenicity of asbestos dust.
• Asbestos is inhaled from asbestos factories (Smith et al. 1972).
• Asbestos have greater fibrinogenic and carcinogenic properties in comparison to other minerals (Manning, 2002).

Pathogenesis:

• There are two major hypotheses to explain how asbestos fibers induce a fibrogenic response. One is the oxygen radical hypothesis and the other is the growth factor hypothesis.
• The bio reactive oxygen species and their cytotoxic metabolites are produced extracellularly on fibers surfaces and/or intracellularly as a result of interactions with various lung cells.
• Generation of oxidants by fibers due to their surface redox properties or upon interaction and uptake of fibers by cells or by inflammation.
• There is increasing evidence that molecules such as platelet-derived growth factor and transforming growth factor, both synthesized and secreted by activated lung macrophages, are responsible, respectively, for the increased interstitial cell populations and extracellular matrix proteins that are the hallmarks of asbestos-induced fibrosis (Brody, 1993).
• In the case of a long fibre, which is too big for removal by phagocytosis and is not expectorated, the reaction is an intra-alveolar deposition of connective tissue. This results in a nodular distribution of fibrous tissue (King et al. 1946).
• With shorter fibres capable of being mobilized into the alveolar walls and lymphatics the fibrous tissue is laid down in the alveolar walls, which ultimately leads to diffuse interstitial fibrosis (King et al. 1946).

Macroscopically:

• The pleura is thickened and the lungs are firm (Smith et al. 1972).

Microscopically:

• Asbestos occur as fine, white anisotropic fibers and as “asbestos bodies”. Asbestos bodies are long beaded rods with rounded ends, which are yellow due to an iron coating that can be demonstrated with the Prussian blue reaction. Asbestos bodies are isotropic (dark under polarized light). Further asbestos incite fibrous scarring of the pleura, around bronchioles and alveolar ducts and within alveolar septae. Moreover Discrete nodules as in silicosis do not develop. Foreign body giant cells may form adjacent to the asbestos particles (Smith et al. 1972).
• The alveolar walls exhibited focally increased cellularity and an increase in argyrophilic fibers. Numerous alveolar macrophages and giant cells were seen among and around the filamentous dust (Paul Gross et al.1967).

Diseases caused by asbestos:

• Inhaled asbestos fibers caused:

(1) asbestosis, a diffuse fibrosis in the nonciliated portion of the lung;

(2) lung cancer; and

(3) mesothelioma, a cancer of the pleura and peritoneum

(Morton Lippmann, 1988).

1) Asbestosis: Bilateral diffuse interstitial pulmonary fibrosis involving the lower zones of the lungs with severe disease closer to the pleura. In advanced asbestosis, honeycombing is common. Discrete foci of fibrosis in the walls of respiratory bronchioles associated with the presence of asbestos bodies or fibers which are coated with iron and protein.

2) Pleural plagues: Pleural plaques are hallmark of asbestosis and appear as white or yellow smooth surfaced lesions on parietal, visceral and diaphragmatic pleura. Microscopically, pleural plaques are acellular, nonvascular dense strands of hyalinized collagen showing a ‘‘basket-weave’’ pattern of mesh appearance.

3) Bronchogenic carcinoma: The presence of asbestosis and the severity and extent of exposure required for an excess lung cancer risk.

4) Mesothelioma: There is an increased prevalence of pleural mesothelioma and lower prevalence of peritoneal mesothelioma in asbestos-exposed workers. Malignant mesothelioma rapidly spreads over the surfaces of the lung, thoracic, and abdominal cavities.

Diffuse malignant mesothelioma:

There are basically “three hypotheses” regarding the pathogenesis of asbestos-induced DMM, which may be summarized as follows:

(1) The “oxidative stress theory” is based on the fact that phagocytic cells that engulf asbestos fibers produce large amounts of free radicals due to their inability to digest the fibers, and epidemiological studies indicating that iron-containing asbestos fibers appear more carcinogenic;

(2) The “chromosome tangling theory” postulates that asbestos fibers damage chromosomes when cells divide; and

(3) The “theory of adsorption of many specific proteins as well as carcinogenic molecules” states that asbestos fibers in vivo concentrate proteins or chemicals including the components of cigarette smoke.

(Shinya Toyokuni, 2009

1. Byssinosis

• Definiton: Byssinosis is a lung disease caused by occupational exposure to dust from cotton, hemp or flax.
• Synonym’s: Other names for byssinosis include Monday fever, brown lung disease, mill fever or cotton workers’ lung
• Sickness caused by respiratory disorders is frequent in cotton mill operators therefore referred to as “stripper’s asthma” or “cotton-mill fever”.

Pathogenesis:

• Inhalation of endotoxin produced by gram negative bacteria in the fibers of cotton may stimulate inflammation that damages the normal structure of the lung.
• It causes the release of histamine, which constricts the air passages. As a result, breathing becomes difficult.
• Over time the dust accumulates in the lung, producing a typical discoloration that gives the disease its name Brown lung disease.

Microscopically:

• Pathologically there is chronic bronchitis, and, in many series, emphysema is also present.

Significance and result:

• Byssinosis is generally not serious.
• But if left untreated it can lead to chronic illnesses such as emphysema and chronic bronchitis.
• When exposure of fiber stop, the illness will clear up.
• In case of long-time exposure there is irreversible damage to lungs.

1. Talcosis

• Talc is a hydrated magnesium silicate used in the leather, ceramic, paper, plastics, rubber, building, paint, and cosmetic industries (Lucía Flors, 2010).

Macroscopically:

• Talc causes a non necrotizing granulomatous inflammation that leads to progressive fibrosis.
• Inhaled particulates produce small centrilobular and subpleural nodules, lobular emphysema in lower lobes.

Microscopically:

• Striking appearance of birefrigerent, needle shaped particles of talc seen within the giant cells and in the areas of pulmonary fibrosis (Marchiori et. al., 2010)
• Late complication includes chronic respiratory failure, emphysema, pulmonary arterial hypertension, cor pulmonale.

1. B) Other exogenous pigmentation:
2. Plumbism:

• Definition: Plumbism is the pigmentation of tissue resulting from the presence of bot lead and hydrogen sulfide in the tissue (Runnells et al. 1965).
• Chronic poisoning by lead is known as plumbism (Ganti Sastry, 2001)
• Animal lead poisoning(also known as avian plumbism, or avian saturnismfor birds)

Lead sources:

• As the lead and lead salts present in batteries are readily eaten by livestock animals, they are the most common source of lead poisoning.
• Especially in calves, paint is the usual source of the lead (Runnells et al. 1965).
• There are many potential sources of lead including contaminated feed or soil, lead paint, plumbing solder, lead shot, grease, discarded asphalt, and crankcase oil (CDFA, 2016).
• Water passing through lead pipes may dissolve enough of the element from the pipes to cause poisoning and pigmentation of tissues (Runnells et al. 1965).

Animal susceptibility:

• Cattle and poultry are most at risk of lead poisoning because they are inquisitive.
• The risk of lead toxicity can also increase during drought. Hungry livestock may develop pica (consumption of non-food items), particularly if concurrently suffering trace element or mineral deficiencies.
• Low pasture cover may increase the likelihood of livestock finding hazardous materials (CDFA, 2016).

Pathogenesis:

• It is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductiveand nervous It mainly affects the haematopoietic system.
• Once the Pb moves across the alveolar barrier, it enters the bloodstream and its distribution depends on the specific affinity of the components of different tissues (Rendón, et al. 2018)
• It affects the sulfhydryl group containing enzymes and also thiol content of erythrocyte, antioxidant defences and tissues rich in mitochondria.
• It inhibits the delta amino levaminic acid dehydrogenase enzyme (ALA) present in the  Hence toxic to young animals, mainly dogs and cattle.
• The caustic action of lead salts causes gastroenteritis.

Macroscopically:

• Pigmentation is observed at the “gum line (lead line)” where the lead in the tissues comes in contact with the hydrogen sulphide produced by putrefactive bacteria found around teeth (Ganty Sastry, 2001)
• Lead particles are found in the reticulum of affected ruminants or within the crop of poultry (CDFA, 2016).
• Lead in intestinal tract causes the feaces to have grey black colour. Further the intestinal mucous membrane becomes grey in colour (Runnells et al. 1965).
• In the nervous system, oedema, congestion of the cerebral cortex, flattening of the cortical gyri are present (Blakley, 2022).
• Symptoms of hemopoietic system involvement include microcytic, hypochromic anemia with basophilic stippling of the erythrocytes (Papanikolaou et al. 2005).

Microscopically:

• Lead is not observed in tissue when routine haematoxylin and eosin preparations are made. Special staining techniques or chemical analysis must be used to demonstrate the element. (Runnells et al. 1965).
• Endothelial swelling, laminar cortical necrosis, oedema of the white matter may be present.
• Tubular necrosis and degeneration and intranuclear acid fast inclusion bodies are seen in kidney.
• The presence of an infiltrate of mononuclear cells surrounding the portal triads and necrotic changes in the hepatocytes are observed (Mani et al. 2007).

Significance and result:

• The grey or black areas where hydrogen sulphide is present is an indication of presence of lead (Runnells et al. 1965).

1. Tattooing:

• Definition: Tattoos are characterized by introduction of exogenous pigments into the dermis.
• The body responds to tattooing with initial sloughing of the overlying epidermis, variable dermal inflammation, gradual assimilation of the pigment into macrophages.
• In tattooing the pigment particles are transported by the macrophages to the connective tissue in the carium and deposited there.
• This pigment is not found in epithelial cells. The phagocytes may also transport and deposit the pigment in the regional lymph nodes.

Microscopically:

• Identification of a tattoo is not difficult; brown, black, yellow, red pigments are readily visualized in the tissue section. Pigments have tendency to lie in the loose fibrous tissue surrounding blood vessels in the superficial and mid dermis. They also tend to cluster as dense aggregates in the papillary dermis and in general may be with in macrophages or extracellularly between collagen bundles (AP Goldstein, 1979).
• Dermatologic adverse reactions are relatively uncommon and they include infections, immune mediated reactions, cutaneous lesions secondary to the Koebner phenomenon, exacerbation of prexisting dermatosis, benign and malignant neoplasms (Castro et al. 2022).

III. Argyrosis

• Argyrosis is the ashen grey pigmentation of the skin, conjunctiva, internal organs which results from administration of excessive amount of silver compounds over a long period of time (Runnells, et al. 1965).
• Silver was commonly used at one time in the treatment of various chronic disease.
• This condition is noticed in long continued therapy with silver salts which is deposited on finely granular albuminate.
• The skin and conjunctiva become grey or grey blue. Internal organ may show similar pigmentation.
• Pigmentation is not intracellular. It is deposited in the cement substance. In skin it found in dermis just under the epidermis while in the kidneys it is deposited in the lamina densa of glomeruli and outside the tubular epithelium.
• The black granular deposits are found in kuffers cells and ground substances of the arteriolar and venules of the liver.
• No harm appears to be caused except the disfigurement for the face of man is grey or ash coloured and this is permanent blemish.

1. Kaolin

• Synonyms: Also known as China clay or Fullers earth.
• Kaolin is a kind of clay derived by disintegration of an aluminous material such as feldspar or mica.
• The essential mineral constituent is hydrated aluminium silicate (kaolinite) but the following elements may also be present: silicon, aluminium, iron, titanium, calcium, magnesium, potassium water, carbon, and organic matter.
• Kaolin has been incriminated as a cause of pneumoconiosis (Kaolinosis) in man which leads to dense pulmonary scarring.

Macroscopically:

• It has also produced extensive subcutaneous granulomas in the pharyngeal and neck tissues of animals following over zealous administration of various kaolin containing products for gastrointestinal disease.
• The kaolin accidentally introduced into the subcutaneous tissue incites a striking influx of macrophages producing dense nodules which displace adjacent tissues.

Microscopically:

• The kaolin is visible as amorphous material and fine anisotropic crystals within macrophages.

 

(Runnelle, et al. 1965)

                           

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