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Created page with " ==Exogenous Pigmentation== * Enter body from environment ===Carbon (Anthracosis)=== * This occurs where carbon particles are inhaled over a long period of time. * Carbon part..."

==Exogenous Pigmentation==

* Enter body from environment

===Carbon (Anthracosis)===

* This occurs where carbon particles are inhaled over a long period of time.
* Carbon particles are phagocytosed by alveolar [[Macrophages|Macrophages]].
** Are carried to a peribronchiolar location and the local bronchial [[Lymph Nodes - Anatomy & Physiology|lymph nodes]].
* It is common in animals that live in cities.
** There is air pollution due to smoke.
** Mostly seen in dogs.
* Can occur in the mesenteric [[Lymph Nodes - Anatomy & Physiology|lymph nodes]] of pigs that feed on ash heaps.
* Carbon is insoluble and results in minimal irritation.

====Gross Appearance====

* Black or grey speckles in lungs.

====Histological Apprearance====

* Black extra- or intra-cellular granules .
** Resistant to solvents and bleaching agents.
** Can cause slight fibrosis in alveolar walls.

===Pneumoconiosis===

* A serious pigmentation.
* Results from repeated inhalation of irritating mineral dust, e.g.
** Coal
** Silica
** Asbestos
* Leads to pulmonary fibrosis.
** Varying shades of grey.
* Asbestos may also cause pulmonary, pleural and peritoneal [[Neoplasia - Pathology|tumours]].
* Seen more in man than animals.
** Occupational hazards.

===Carotenoids===

* Also known as lipochrome.
* Carotenoids are fat-soluble greenish-yellow pigments that bind to lipids in body.
** Derived from carotenes and xanthophyll in plants.
** Can be seen grossly in a number of normal places
*** Adrenal cortex.
*** Testes.
*** Corpus luteum.
*** Liver.
*** Yolks of eggs.
*** Fat of horses and Channel Island cattle.
* May be confused with a [[Pigmentation and Calcification - Pathology#Jaundice|jaundiced]] liver or subcutis.
** Adding minced tissue to a mixture of ether and water can distinguish the two.
*** Carotenoids are fat-soluble and dissolve in the ether fraction.
*** Bile pigments dissolve in the water fraction.

===Iatrogenic===

*E.g.
** Iron injections in piglets.
** Coloured antiseptics.
** Tattooing.

==Endogenous Pigmentation==

* Pigments are formed inside the body.

===Melanin===

* Normally gives visible colour to the skin, hair, and iris.
* Melanin synthesis is controlled by melanocyte stimulating hormone (MSH).
** MSH is produced in the pituitary.
** Melanin is derived from tyrosine (an amino acid) utilising a copper-containing enzyme, tyrosinase.
* Melanosis occurs when excessive quantities of pigment are deposited in internal organs.
** The lungs and aorta, pleura, brain and meninges, and [[Liver - Anatomy & Physiology|liver]] are often affected.

====Gross Appearance====

* Black/brown pigmentation is seen, either as spots or as larger areas.
** Larger areas can give the lungs or [[Liver - Anatomy & Physiology|liver]] a chequer-board pattern.
* No change in structure occurs.

====Histological Appearance====

* Round granules of brown/black are seen in the cytoplasm of cells.
** Can be bleached out by chlorine or KMNO<sub>4</sub>.
** Stain black with silver stain Masson Fontana.

====Significance====

* There is no significance of melanosis when it occurs in the internal organs.
* There is also no significance in hyperpigmentation of the skin.
* Melanosis may be associated with chronic irritation.
** For example, in wound healing.
*** [[Healing and Repair - Pathology#Scarring|Scars]] are pigmented.
* Hyperpigmentation may be significant in excess cortisol states such as [[Adrenal Glands - Pathology#Adrenal Hyperfunction|Cushing’s Disease]].
** There may be tumours of melanocytes.
* Albinos have no pigment in their hair or skin, and have pink irises.
** Lack sufficient tyrosinase enzyme in their melanocytes.
** Albino rabbits, rats and mice are seen.

===Blood Pigments===

* Blood pigments causing pigmentation may be
** Normal derivatives of haemoglobin, which have accumulated in excess.
*** Haemosiderin.
*** Bilirubin.
** Pathological
*** Methaemoglobin (chocolate brown) in nitrate poisoning.
*** Carboxyhaemoglobin (bright cherry red) in carbon monoxide poisoning.
*** Parasitic acid haematin.

====Haemoglobin====

* Results from excessive phagocytosis or haemolysis of red blood cells.
** Haemoglobin is freed into the plasma which becomes red.
* If there is sufficient haemolysis, the haemoglobin overspills into the urine.
** Haemoglobinuria.
*** Both the kidneys and the urine appear dark red.
* Can be caused by a variety of agents including:
** Bacteria
*** E.g. [[Leptospira|''Leptospira'']]
** Protozoa
*** E.g. [[Babesia|''Babesia bigemina'']]
** Chemicals
*** E.g. excessive copper in the liver of sheep.
** Immune mediated conditions
*** E.g. autoimmune mediated haemolytic anaemia.
* Haemoglobin is not usually seen in the tissues.

====Haemosiderin====

* Haemosiderin is a golden brown/yellow pigment.
** Derived from splitting haemoglobin into an iron-porphyrin compound and globulin.
*** This splitting occurs when ageing red blood cells are engulfed by [[Macrophages|macrophages]] in the [[Spleen - Anatomy & Physiology|spleen]], [[Lymph Nodes - Anatomy & Physiology|lymph nodes]], [[Bone Marrow - Anatomy & Physiology|bone marrow]] and [[Liver - Anatomy & Physiology|liver]].
**** The iron containing fragment remains in the [[Macrophages|macrophages]] and is recycled to make more haemoglobin.
* Excessive quantities of haemosiderin arise from increased red cell breakdown by:
** Phagocytosis
** Haemolysis
* Large amounts of haemosiderin diffusely spread throughout the [[Spleen - Anatomy & Physiology|spleen]] usually indicates a haemolytic disorder.
* Local production of haemosiderin is responsible for the appearance of bruising in injury.
** Other haemoglobin breakdown products are also formed.
* Haemosiderin also accumulates in chronic congestion of the vascular system due to heart failure.
** Seen in highly vascular tissues such as the lung, [[Liver - Anatomy & Physiology|liver]] and [[Spleen - Anatomy & Physiology|spleen]].

=====Gross Appearance=====

* Grossly, very little can be seen unless there has been substantial breakdown of haemoglobin.
** In this case the organ may appear brownish.
* Also seen as bruising.
* Usually not appreciable in the lung in heart failure.
* In repetitive exercise induced pulmonary [[Haemorrhage|haemorrhage]] of horses, the affected area of the dorsal lung may be brownish in colour.
* The equine [[Liver - Anatomy & Physiology|liver]] often contains stores of haemosiderin giving them a brownish colour.

=====Histological Appearance=====

* Accumulates in the cytoplasm of macrophages.
* Chronic congestion in the lung can be seen due to heart failure.
** Some of the red blood cells escape out of the alveolar capillaries and are engulfed by alveolar macrophages.
*** Called "heart failure" cells.
* Prussian blue stains specifically for haemosiderin.
** Granules stain blue.

====Haematin====

* There are 2 types of haematin.
** Acid haematin
** Parasitic haematin.

=====Acid Haematin=====

* A pigment artefact.
* Acid in unbuffered formalin binds with haemoglobin to form a brownish-black granular pigment.
* Only seen microscopically.
* Can be formed in areas of ante-mortem ulceration of the stomach.
** There is increased acidity due to hydrochloric acid.
* Acid haematin is iron negative.
* Must remove acid haematin prior to staining sections to allow haemosiderin to be distinguished.
** A useful clue in the untreated section is the presence of the pigment in the red blood cells of vessels.

=====Parasitic Haematin=====

* Certain parasites in other parts of the world (e.g. [[Trematodes|''Schistosoma'' sp.]]) take up blood.
** Break haemoglobin to haematin.
** Regurgitate the pigment back into circulation.
*** Taken up by macrophages, which go the [[Lymph Nodes - Anatomy & Physiology|lymph nodes]], [[Liver - Anatomy & Physiology|liver]] and [[Spleen - Anatomy & Physiology|spleen]].
* [[Trematodes|''Fasciola hepatica'']] in this country causes chronic damage to the bile ducts of the bovine [[Liver - Anatomy & Physiology|liver]].
** Produces acid haematin, which lines the bile ducts.
** The fluke and its spines damage the duct lining and feed on blood liberated from the blood vessels.
*** This is regurgitated by the fluke and passes down the bile duct to the intestine together with the proteins liberated.
**** This parasitic haematin is in an un-resorbable form, and so the flukes lead to hypoproteinaemia and anaemia.

====Jaundice====

* Jaundice is also known as icterus.
* Jaundice is a yellowish discoloration due to excessive levels of bilirubin in plasma.
** Seen in tissues that are normally white, e.g.
*** Fat
*** Intima of blood vessels
*** Sclera
* Bilirubin stains brown with H&E, like both haemosiderin and lipofuscin.
** Must be distinguished from each other by special stains.
*** Bilirubin stains bright green with a Fouchet stain.

=====Production of Bilirubin=====

* Red blood cells either undergo:
** Phagocytosis, in the case of ageing cells.
** Haemolysis, in haemolytic crises.
* Haemoglobin is freed from the red cells and is further broken down in the reticulo-endothelial system to haeme and globulin.
** Haeme is a mixture of iron and porphyrin.
** Both the iron and globulin are recycled for further use in erythropoiesis.
* The porphyrin from haemoglobin breakdown is converted to biliverdin.
** A green pigment
*** May contribute to the greenish appearance seen in local bruising.
* Biliverdin is subsequently changed into bilirubin.
* The bilirubin is then bound to albumin, and transported in the blood to the [[Liver - Anatomy & Physiology|liver]].
** In the hepatocyte, bilirubin is released from the albumin and conjugated with glucuronic acid.
*** Forms conjugated bilirubin.
**** Excreted into the intestine via the bile ducts.

===== Prehepatic (Haemolytic) Icterus=====

* Due to excessive production of bilirubin due to haemolysis, e.g.
** [[Babesia|Babesiosis]]
** [[Leptospira|Leptospirosis]]
** Copper poisoning in sheep.
* There is excessive unconjugated bilirubin in the blood.

=====Hepatic (Toxic) Icterus=====

* Due to [[Liver - Anatomy & Physiology|liver]] cell damage.
** In hepatocytic [[Necrosis - Pathology|necrosis]], the liver cannot conjugate bilirubin.
*** Results in increased levels of unconjugated bilirubin in the blood.
** In less severe damage, the hepatocytes swell and bile caniculi are pressed closed.
*** There is therefore intrahepatic obstruction conjugated bilirubin accumulated in the blood.
* In reality, these situations occur together.
** There is both excessive unconjugated and conjugated bilirubin in the blood.
* Examples:
** [[Leptospira|''Leptospira icterohaemorrhagica'']] in the dog.
** Rift Valley fever virus.
** Some plant poisonings.
*** Lantana.
** Some fungal infections.
*** Aflatoxicosis.

=====Post-Hepatic (Obstructive) Icterus=====

* Due to the flow of bile being obstructed, for example by:
** [[Biliary Tract - Obstruction|Gallstones]]
** [[Parasites|Parasites]]
*** [[Ascaris suum|''Ascaris suum'']] in the bile ducts of pigs.
** [[Neoplasia - Pathology|Tumours]]
*** Adenocarcinoma of pancreas presses upon and occludes the bile duct.
* Results in excessive conjugated bilirubin in the blood.
* Constructive icterus causes, out of the three types of icterus,
** The most elevated levels of bilirubin in the blood
** The greatest discoloration of the tissues of the body.

=====Van de Berg Test=====

* This test can distinguish between the different types of jaundice, based on whether the bilirubin is conjugated or not.
* Plasma from the jaundiced animal is treated with an aqueous solution of a reagent (diazotised sulphanilic acid).
** Gives a red-purple colour.
*** The intensity of this colour is directly proportional to the amount of water-soluble (i.e. conjugated ) bilirubin in the sample.
** Further addition of alcohol intensifies the colour if there is non-water-soluble (i.e. unconjugated) bilirubin also present.
*** The intensified colour is directly proportional to the total amount of bilirubin present in the sample.
** The difference between the two readings gives the amount of unconjugated bilirubin in the sample.

====Haematoidin====

* Haematoidin is bile pigment laid down in areas of focal haemorrhage where red blood cells are lysed.
** I.e. it is unconjugated bilirubin in tissues.
* Has a clear yellow colour.
* Can sometimes be granular.
** Could be confused with haemosiderin.
*** Unlike haemosiderin, haematoid does not contain iron.
**** Does not stain with Prussian Blue.

====Porphyria====

* Porphyrin is a component of haeme.
* Porphyria is a rare heritable condition in cattle, pigs and cats, where there is imperfect synthesis of porphyrin.
** Due to defective enzymes.
** Leads to a degree of anaemia in affected animals.
* Porphyria is best-documented in cattle.
** Porphyrins (brownish in colour) accumulate in bone, [[:Category:Teeth - Anatomy & Physiology|teeth]] and other internal tissues.
** Excess porphyrins also circulate in the blood stream and are excreted in the urine.
** Urine has a reddish colour.
* Porphyrin is a fluorescent pigment.
** Urine will also fluoresce under ultra-violet light.

=====Histological Appearance=====

* Brown granular pigment that looks like haemosiderin but is iron negative.
* Found in [[Macrophages|macrophages]] of [[Bone Marrow - Anatomy & Physiology|bone marrow]], [[Liver - Anatomy & Physiology|liver]], lungs, and [[Lymph Nodes - Anatomy & Physiology|lymph nodes]].

=====Photosensitisation=====

* Porphyrin is a fluorescent pigment.
** Is related to chlorophyll.
* UV light acts on porphyrins as they circulate in the blood under the white skin.
** Changed to a longer wavelength.
*** Causes [[Acute Inflammation|acute inflammation]] in the skin.
* The inflammation caused may look like sunburn, but is actually a necrotising dermatitis.
** Affected areas slough off.
** Large areas of the dermis are exposed to infection.
** Death due to toxaemia can ensue if it is severe.
* Removing animals from sunlight causes the lesions to regress.


* The most common and important form of photosensitisation in animals is due to [[Liver - Anatomy & Physiology|liver]] damage coupled with a diet containing a lot of chlorophyll.
** I. e. animals on green pasture.
* A wide variety of plants and fungi have been implicated in causing acute toxic damage to the [[Liver - Anatomy & Physiology|liver]].
** Including grasses, clovers and Brassica sp.
** This [[Liver - Anatomy & Physiology|liver]] damage may cause the imperfect breakdown of chlorophyll and raised phyloerythrin levels.
*** Causes photosensitisation.
* The common form in sheep is facial eczema.
** The face and head are swollen, raw and bleeding.


* A third form of photosensitisation occurs in the absence of [[Liver - Anatomy & Physiology|liver]] damage and is due to certain plants containing excessive fluorescent pigments, e.g.
** Buckwheat (Fagopyrum esculentum)
** St. John’s wort (Hypericum perforatum)

===Lipofuscin===

* A yellow-brown granular pigment composed of lipid, phospholipid and protein polymers.
** Thought to be derived from the lipid peroxidation of cellular membranes.
* Lipofuscin is the ageing pigment.
** Can be seen in senile animals in
*** [[Muscles Degenerative - Pathology#Pigmentation|Muscle]]
**** E.g. in "[[Disorders of Cell Growth - Pathology#Brown Atrophy|brown atrophy]]".
*** Myocardium
*** Neurones (particularly those of horses)
*** Normal liver of middle-aged cats.
* '''Xanthosis''' is when lipofuscin is a prominent feature in the tissues of Ayrshire cattle.
** Lipofuscin is found in the heart, diaphragm, masseter muscles, kidney and adrenal cortex.
* Pathologically, lipofuscin is associated with Vitamin E/ Selenium deficiency.
** There is excessive lipid peroxidation of cellular membranes by free O<sub>2</sub> radicals.

====Gross Appearance====

* '''Xanthosis''' - gives a brown colour to the organ.
* '''Senility'''
** May impart a brownish colour to the heart.
*** Sometimes called ‘brown atrophy’.
** In other areas, lipofuscin is only visualised microscopically.

====Histological Appearance====

* Granular
* Brown- yellow in colour.
* Lies in the cytoplasm...
** ...At either end of the nucleus in the heart.
** ...Scattered throughout in the [[Liver - Anatomy & Physiology|liver]] and neurones

====Ceroid====

* Is a variant of lipfuscin.
* Stains acid fast.
* Occurs in:
** Hepatocytes
*** E.g. in choline deficiency in cirrhosis
** [[Macrophages|Macrophages]]
** A variety of tissues including fat, cardiac muscle, splenic trabeculae and intestine in Vitamin E deficiency.
*** Sometimes being so prominent as to be grossly visible.
**** Yellow fat disease
***** Pigs and cats
**** Brown gut
***** Dogs

[[Category:General Pathology]]
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