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Pathologic Pigmentation

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Pathologic Pigmentation Pathologic pigmentation 2nd October 2019 Topics • 32. Pathologic pigmentation caused by hemoglobin and haemosiderin • 33. Pathologic pigmentation caused by hematoidin, and bilirubin • 34. Pathologic pigmentation caused by porphyrins • 35. Pathologic pigmentation caused by melanin, lipofuscin, and ceroid • 36. Exogenous pigments • 37. Concretions (lithiasis) and pseudoconcretions Pigments Forms: • Endogenous pigments – haemoglobinogenous pigments • haemoglobin – szulfmethaemoglobin, haemiglobin, carbon- monoxid-haemoglobin, formaldehyde pigment, haematin • haemosiderin • haematoidin and bilirubin • porphyrin – anhaemoglobinogenous (autochtonous) pigments • Exogenous pigments 32. Pigmentation caused by haemoglobin and haemosiderin • Haemoglobin – Haemolysis haemoglobinaemia – Haemoglobin cylinders in renal tubuli (benzidine +) • Causes of haemolysis: – Autointoxication – Chemicals (arsenic, copper, phenol, trichlorethane) – Drugs (sulphonamides, atebrin, phenacetin) – Physical effects (radiation, thermal injuries) – Bacteria, viruses, parasites (Babesia) – plant poisons Hemoglobin forms: • Sulfhaemoglobin (H2S): greenish fades • Methaemoglobin (Fe++, - Fe+++): dark brown • Carboxi-haemoglobin (CO-intoxication) – cherry pink discoloration, clearly visible in brain • Hemosiderin – Brown, amorphous, granular, iron-containing pigment – Develops in RES cells (macrophages) – Siderin: injection of iron-dextran preparates – Histology: • Prussian blue (Perl’s reaction) • Turnbull’s technique – Local haemorrhages: siderophor cells – Pseudomelanosis: hemosiderin + H2S (putrefaction) Hemosiderin – Pseudomelanosis: hemosiderin + H2S (putrefaction) 33. Pigmentation caused by hematoidin and bilirubin • Hematoidin – Brownish pigment – Old haemorrhages – Iron free derivate of haem! – Needle-shaped or rhomboid crystals • Bilirubin (biliverdin: oxydized): bile pigment – RHS (MPS) cells (indirect bilirubin) – Liver cells (direct bilirubin – conjugated to glucuronic acid) Simultaneous presence of haematoidin and haemosiderin in subcutaneous tissue Jaundice - icterus • Bilirubin in tissues: solute and precipitated to proteins • Staining the tissues yellow (conjunctiva, sclera, intima of blood vessels…) • Bird liver: green (biliverdin) • Staining: – Forsgren method (reddish-blue) Jaundice - icterus • Posthepatic • (stagnation or resorption) – Obstruction to the outflow of bile (bilirubin I) – In the blood and urine: bilirubin II • Prehepatic (hyperfunctional or hemolytic) – Intensive haemolysis – (bilirubin I in blood) – Icterus neonatorum • Hepatic (toxic or retention) – (bilirubin I and bilirubin II) – In the urine: bilirubin II, urobilinogen – Cell necrosis Cholelithiasis ( posthepatic icterus) Intrahepatic accumulation of bilirubin HE; 200x HE; 600x 34. Pathologic pigmentation caused by porphyrins Porphyria • Porphyrin – Haem synthesis – Protoporphyrin + Fe + globulin = Hb – Porphyrin synthesis: liver + bone marrow – Affinity to bone – Photosensitization – Brownish-violet, fluorescence under UV light – Uro- and coproporphyrin = excreted with urine and faeces – Hereditary porphyria – Toxicoses: lead, arsenic, CCl4, benzene, anilin • coproporphyrin Porphyria • Hereditary • Toxicoses (Pb, As, anilin etc.) • Spongy bones are coloured • Dental cement brown • Dentin pink, reddish-brown • Enamel: white • Cartilage, ligaments, tendons: uncoloured 40. HGCE - Pyometra complex 35. Pathologic pigmentation caused by melanin, lipofuscin and ceroid Autochton pigments Pigments Forms: • Endogenous pigments – haemoglobinogenous pigments • haemoglobin – szulfmethaemoglobin, haemiglobin, carbon- monoxid-haemoglobin, formaldehyde pigment, haematin • haemosiderin • haematoidin and bilirubin • porphyrin – anhaemoglobinogenous (autochtonous) pigments • Exogenous pigments Anhaemoglobinogen pigments • melanin • lipofuscin • ceroid • ceroid-like pigment 35. Pigmentation caused by melanin, lipofuscin and ceroid Autochtonous (non hemoglobinogen pigments) Melanin • Insoluble in water, acids, fat solvents • Solubile in K-OH, Na-OH • H2O2 – bleach • Ectodermal origin cells produce it • Tyrosinase enzyme initiates melanin synthesis • Melanocyte-stimulating hormone (MSH) stimulates, but also ACTH has influence on the pigmentation • Brownish-blackish pigment – no iron Melanocyte Melanin • Produced by: melanocytes • Stored by: melanophags tirozin Tirozinase (oxidation) melanin Hypophysis (MSH, ACTH) Under physiological conditions • skin – epidermis, corium • during pregnancy – nipples, face, middle line if the belly (chloasma gravidarum) • eye – retina, iris, chorioid • ganglion cells – nucleus niger • leptomenings • mucous membrane of the oral cavity • mammary gland in special swine breeds (Berkshire) • Serous membrane of reptils and some birds Three variations of abnormal pigmentation • Hyperpigmentatio – Radiation, arsenic treatment – Naevi (naevus pigmentosus) – Focal melanosis – Melanoma – Acanthosis nigricans – Addison’s disease • Hypopigmentatio – Leukoderma (surgical treatment) – Vitiligo (pigmentfree area) • Albinismus Melanosis maculosa Melanoma benignum (melanocytoma) Acanthosis nigricans • Disease of unknown origin • Hyperpigmentation of the axillae, ventral thorax, inguinal and circum-anal region • Uneven proliferation of the epithelial cells in stratum spinosum • Skin thickened, surface uneven • Velvety touch Hypopigmentation • Age • Vitiligo (hamartia) • Leukoderma (focal absence after injury) • Trophoneurotic problems – dourine in horses • Trypanosoma equiperdum infection – depigmented areas • pale areas after maceration • Albinism – pathological absence of melanin – congenital in rodents • Lipofuscin Golden-brown pigment protein + lipids, no iron Formed in lysosomes Ageing cells Autooxidation of unsaturated lipids all three germ layer cells may contain insoluble in water, acid, alkali Liver, kidney tubuli, adrenal gland, chorioid plexus, muscle cells EM: dense, amorphous autophagosomes + granules and lipids Lipofuscin containing histiocytes Lipofuscin in heart muscle cells • Brown bowel syndrome – Dogs – Diarrheal diseases – Steatorrhea – Pancreatic acinar deficiency – Malabsorption – Intestine: brown • Smooth muscle cells • Neuronal ceroid lipofuscinosis – English setter, cattle, sheep, cat – Intracellular accumulation – Progressive loss of cells in the brain and the cerebral function • Ceroid – Lipogenous pigment – Partially oxidized and polymerized unsaturated fatty acid bound to proteins – Produced in macrophages and hepatocytes – Ziehl-Neelsen positive • Yellow fat disease – Alcohol soluble - icterus – Ether soluble - yellow fat disease Ceroid-like pigment yellow Appearance • lipocytes • macrophages • MPS-cells • The fat tissue is yellow – yellow fat disease – cause: high amount if unsaturated fatty acid in the feed Ochronosis (alkaptonuria) • inherited disturbance of the protein metabolism (tyrosine, phenilalanine) amino acids (aromatic) homogentisic-acid oxidation colored substance • Cartilage, tendons, ligaments become greenish • The bones do not get discolorated Pigments Forms: • Endogenous pigments – haemoglobinogenous pigments • haemoglobin – szulfmethaemoglobin, haemiglobin, carbon- monoxid-haemoglobin, formaldehyde pigment, haematin • haemosiderin • haematoidin and bilirubin • porphyrin – anhaemoglobinogenous (autochtonous) pigments • Exogenous pigments 36. Exogenous pigments • Anthracosis – Phagocytic activity against fine coal • Pneumoconiosis – Siderosis (Fe), Chalicosis (CaCO3), – Silicosis, asbestosis, tabacosis… • Tattooing • Pseudoicterus – karotinoids • Medicines – Trypanblue – Silver preparations (argyria)… Exogen pigments • Either colored or non-colored • Enter the body – Aerogenously • pneumoconiosis – Per os (enterogen) • Food, plants (common madder - alizarin) – Skin wound (tattooing) – Parenteral way • In the lungs – Alveolar macrophages + histiocytes – Gets to the regional lymph node Exogen pigments Powders, chemicals, drugs, feed particles • soot, dust = anthracosis • quartz = silicosis • iron = siderosis • lime, whiting = chalicosis • asbestos = asbestosis • tobacco = tabacosis • silver products = argyrosis • karotin = karotinosis (pseudoicterus) • Any substance in the lung - pneumoconiosis Exogen pigments Drug, feed • blackberry = skin, tendons • pannage = fascia, mesenteric lymphnodes • alizarin = osteogenesis – madder (Rubia tinctorum) – fine red dyeplant – used to colour fabric and timber • picric acid = yellow • tripaflavin = yellow • trypan blue = tendons 37. Concretions and pseudoconcretions Lithiasis, calculus formation • Solid substances – From secretions of certain organs – Lined by mucous membranes • Reason for the precipitation – Increased concentration of crystalloids – Decreased protective colloid content • Lithogenous material + binding material → Microlith • calculus, sediment Predisposing factors Lithogenous material in increased amount • Metabolic disorders • Nutritional factors Inflammation of hollow organs • Changes in the pH • Enzymatic destruction of the colloids • Desquamation of the epithelial cells Stasis of excretions Composition of different concretions • Calcium-carbonate – Food is contaminated with limestones • Phosphate calculi – Feeding with forage, bran • Oxalate stones – High amount of fodder beet • Cystine or xanthine stones – Due to metabolic disorders in urinary tract Structure • Microlith – crystallization centre – Foreign body, fibrin, necrotic cells • Lithogenous material – Salts of organic or inorganic acids – Cholestrol, bilirubin, cystine, xanthine • Binding material – Protein or mucous
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