General Veterinary Pathology

ENDOGENOUS PIGMENTS

• These include melanin, lipofuscin, ceroid and haematogenous pigments (Haemoglobin, haemosiderin, porphyrin).

Melanin

Melanin (G. Melas-Black) is a black pigment produced by oxidation of tyrosine to dihydroxy phenyl alanine by the copper containing enzyme tyrosinase in the melanocyte. The melanocytes are generally present in the basal layer of epidermis, retina, iris and pia-arachnoid of black animals and in the oral mucosa (Jersey cows). The melanin pigment protects from ultra ultraviolet radiation.

Pathologically, hypo/ hyper-pigmentation may occur in animals.

• Hypopigmentation
• Copper deficiency in cattle and sheep results in loss of coat colour.
• Albinism: Melanin deficiencies due to lack of tyrosinase. The melanocytes appear normal. Lack of pigmentation in skin, hair, sclera or iris on exposure to sunlight may lead to development of skin cancer.
• Leukoderma is a condition in which local loss of skin pigments which is likely to be seen in the collar, saddle or harness.
• Vitilogo is partial or complete loss of melanocytes in the epidermis.
• Hyperpigmentation
• The condition is found in melanomas and occasionally in malignant melanomas. Gray horses are susceptible to melanomas. Naevus (pigmented moles) is seen in human beings commonly. Focal accumulation of pigments occurs in mammary gland and surrounding fat in gilts and sows.
• Melanosis is a hyperpigmented area sometimes found in the intestine, heart, lung, kidney etc. Melanosis of cornea may lead to blindness in some breeds of dogs e.g. Boxers, Western Terriers. The condition is bilateral and symmetrical. Hyperpigmentation of skin (Acanthosis nigricans) may be associated with chronic injury and hyperadrenalism. The melanocytes contain melanosomes having the pigment. The macrophages laden with melanin are termed as melanophores.
• DOPA reaction

Tissue containing melanocytes convert DOPA to DOPA quinine are tested DOPA positive while melanophores give a DOPA negative test.

Lipofuscin-Ceroid

• Lipofuscin (L. Fuscus-Brown) is known as ‘aging pigment’ or ‘wear and tear pigment’ or ‘biologic garbage’. They are brownish yellow pigments and are accumulated in post-mitotic cells like neurons, cardiomyocytes, skeletal myocytes and in slowly dividing cells like glial cells and hepatocytes. The pigment is intracellular.This pigment cannot be removed by lysosomal degradation or exocytosis. The pigment is a complex of lipid and protein derived from oxidation of polyunsaturated lipids derived from free radical injury and lipid peroxidation. They are referred to as residual bodies representing indigestible residues of autophagic vacuoles. The tissue discolouration is known as ‘brown atrophy’.
• Histochemistry: Fat soluble dyes, acid fast, PAS-positive.
• Ceroid is a pathological pigment. Ceroid is an early form of lipofuscin containing partially oxidised polymerised unsaturated fatty acids. It has got similar chemical component to lipofuscin and occurs in response to severe malnutrition including hypovitaminosis E, cancer cachexia, irradiation and inherited neuronal ceroid lipofuscinosis.The pigment accumulates in Kupffer cells, hepatocytes, skeletal and smooth muscle myocytes. This pigment has a deleterious effect on the cell. Occasionally, the pigments are seen in the small intestine of dogs called intestinal lipofuscinosis and in nutritional panniculitis in cats, minks, foals and pigs (hypovitaminosis E). In cats it is also due to ingestion of fish products which contains highly concentrated unsaturated fatty acids. Hepatic ceroidosis: Salmons and cat fish fed with rancid diets.
• Grossly, lipofuscin pigment gives a brown discolouration to heart and skeletal muscle and thyroid. Lipofuscin in the presence of UV light produces brown fluorescence e.g. thyroid
• Microscopically, light golden brown to dark brown pigments are seen around the perinuclear areas of neurons and different myocytes. This pigment may also be extracellular (feline panniculitis) e.g. autosomal recessive- English Setter dogs

Haemosiderosis

• Haemosiderosis is deposition of haemosiderin in many tissues and organs.
• Haemosiderin is a golden yellow to brown granular crystalline pigments derived from hemoglobin and stored in cells. Normally Hemosiderin is present greatest amount in spleen of horse and least in spleen of dog. 
• Systemic changes
• Localised changes

Causes

• Increased absorption of dietary iron
• Impaired iron utilisation
• Excess haemolysis
• Blood transfusion (Exogenous iron load)

These are occuring as systemic derangement in chronic passive hyperaemia involving lungs where haemorrhages are seen. This erythrocytes are lysed and the haemosiderin is phagocytosed and deposited in the lung. Haemosiderin laden macrophages are called heart failure cells. This along with increased fibrosis gives the lung hardness and brown discolouration. This is referred to as brown induration of lung.

Haemosiderin can also accumulate locally in haemorrhages known as localised haemosiderosis. e.g. Bruishes. A local haemorrhage impart different colours as the wound ages. First it appears red blue. Haemosiderin formed from lysed RBCs are taken by macrophages, red blue colour becomes green blue (Biliverdin formation). Then golden yellow colour haemosiderin deposits.

Microscopically

• Haemosiderin pigments is found in cellular cytoplasm appearing as coarse, granular yellow pigment. Histochemically, it appears blue from prussian blue reaction. It is an insoluble blue black ferric ferrocyanide.

Haemochromatosis

• This condition is due to extreme accumulation of iron in diseases. e.g. Human - Diabetes mellitus associated with hepatic fibrosis. In this iron overload disorder the iron content may reach 50 - 60g when compared to 2 - 3 times more than normal in adult .
• Animals - This may occur due to excessive dietary iron absorption and injection of iron