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Disturbances of pigment metabolismDr Neha MahajanMD Pathology

That impart color to tissues.

Abnormal pigmentation : -excess normalDecrease of normalNormal pigment at abnormal site Abnormal pigment

Pigments: heterogenous group of sub Pigments: heterogenous group of substances

Pigments are coloured substances present in most living beings including humans.

ENDOGENOUS

EXOGENOUS

ENDOGENOUS1.Melanin2.Melanin like pigmentAlkaptonuriaDubin johnson syndrome3.Haemoprotein derived pigmentsHaemosiderinAcid haematin( haemozoin)BilirubinPorphyrins4.LipofuschinEXOGENOUSInhaled pigmentsIngested pigmentsInjected pigments (tatooing)

Endogenous pigments Normal constituents of cells or accumulate under special circumstancese.g MelaninOchronosisHaemoprotein derived pigmentsLipofuscin

MelaninBrown black, non haemoglobin derived pigmentHair, skin, choroid of the eye, meninges and adrenal medulla.Synthesis- in melanocytes and dendritic cells

Stains for melaninFontana silver methodDopa reaction Tyrosinase reaction Florescent microscopy

Disorders of pigmentationHyperpigmentationGeneralisedFocalHypopigmentationGeneralisedFocal

HyperpigmentationGeneralisedAddison`s diseaseChloasmaChronic arsenical poisoningFocalCafeau lait spotsPeutz jegher`s syndromeMelanosis coliMelanotic tumorsLentigo

HypopigmentationHypopigmentation is the loss of skin color. It is caused by melanocyte or melanin depletion, or a decrease in the amino acid tyrosine, which is used by melanocytes to make melanin.

Hypopigmentation

Generalised hypopigmentationAlbinism

Localised hyppopigmentationLeucodermaVitiligoAcquired focal hypopigmentation- leprosy, healing of wounds, DLE,radiation dermatitis

OchronosisAutosomal recessive disorderDeficiency of oxidase enzymeHomogentisic acid- deposited in cartilage,joints, ligaments and tendonsAlkaptonuria- black urine

Haemoprotein derived pigmentsHaemosiderinAcid haematin (haemozoin)BilirubinPorphyrins

HaemosiderinIron is stored in the tissues in 2 forms:FerritinHaemosiderinPrussian blue reactionExcessive storage of haemosiderin Increased breakdown of red cells Systemic overload of iron: primary and secondary haemochromatosis (thalassemia, sideroblastic anaemia, alcoholic cirrhosis, multiple blood transfusions)

Effects of haemosiderin excessLocalised haemosiderosis

Generalised haemosiderosis

Localised haemosiderosis

Haemorrhage in tissue

Bruise or black eye

Brown induration of lung

Infarction

Generalised haemosiderosis( systemic or diffuse)

Two types of patterns:Parenchymatous depostion of haemosiderin- liver, pancreas, kidney and heart.

Reticuloendothelial deposition- liver, spleen, bone marrow.

Causes overload of iron:1.Increased erythropoeitic activity-Haemolytic anaemias,blood transfusions,parenteral iron therapy(ACQUIRED HAEMOSIDEROSIS)2.Excessive intestinal absorption of iron (IDIOPATHIC OR HEREDITARY HAEMOCHROMATOSIS)ADTriad- liver cirrhosis, pancreatic damage & skin pigmentation( bronze diabetes)

Excessive intake of dietary ironBantu`s disease

Haemosiderin golden granules in liver H & E

Prussian blue stain

Acid haematin or haemozoinHaemoprotein derived brown black pigment containing haeme iron in ferric form Cannot be stained by prussian blue reactionSeen in chronic malaria, mismatch blood transfusionFormalin pigment

BilirubinNormal non iron containing pigment present in bileNormal levels < 1mg/dlExcess bilirubin jaundiceClassification Prehepatic Hepatic Post hepaticExcess accumulation of bilirubin pigmenthepatocytes, kupffer cells and bile sinusoidsKernicterus

BILIRUBIN METABOLISM

Normal Bilirubin Metabolism

Jaundice

Hyperbilirubinemia:Two forms:Direct bilirubin: Conjugated with glucoronic acidIndirect bilirubin: unconjugated, insoluble in water.

PrehepaticHepaticPost hepaticBasic mechanismHemolysis leading to increased productionDeficient uptake,c onjugation or excretion by hepatocytesDeficient excretion due to obstructionType of bilirubin raisedMainly unconjugatedUC +C BothMainly conjugatedUrine bilirubinabsentpresentpresentUrine urobilinogenPresent VariableDecreasedPrototypeHaemolytic anemiaViral hepatitisCommon duct stonePTNormalAbnormal not corrected with vit KAbnormal corrected with vit KAdditionalFeatures of hemolysis on blood smearMarked rise of sr ALT & ASTMarked rise of sr ALP >3 times

PorphyriasPorphyrins are tetrapyrroles which exists in 3 forms:Haeme contains iron.Chlorophyl contains magnesiumCobalamin contains cobaltPorphyria--- genetic deficiency of one of the enzymes required for synthesis of haeme, so there is excess production of porphyrins.Genetic deficiency is precipitated by intake of drugs

Glycine + Succinyl CoA

Enzyme: ALA Synthase STEP 1 PLP

d-Amino levulinic acid (ALA) Enzyme: ALA dehydratase. STEP 2 porphobilinogen

FURTHER STEPS Protoporphyrin IX

Ferrous ion (Fe2+ ) introduction of iron Enzyme: ferrochelatase heme

Summary of biosynthesis of heme

Porphyrias ErythropoeiticDefective synthesis of haeme in RBC`sCongenital: red urine due to presence of uroporphyrin I and coproporphyrin I.Skin highly photosensitive, red brown discolourationErythropoeitic: excess of protoporphyrin but no excess of porphyrin in urine.

HepaticDefective synthesis of haeme in liver.Acute intermittent porphyria: acute episodes of 3 patterns: abdominal, neurological and psychotic, no photosensitivityExcess delta aminolaevulinic acid and porphobilinogen in urine

Variegate porphyriaPhotosensitivity.Acute attacks of colicky abdominal pain & neurological manifestations.Hereditary porphyriaPorphyria cutanea tardaMost common of all porphyrias.Porhyrins collect in liver & small quantity excreted in urine.Haemosiderosis----cirrhosis---- hepatocellular carcinoma.

LipofuschinWear and tear pigment.Yellowish brown intracellular pigment.Pigment found in atrophied cells of old age. Seen in myocardial fibres, hepatocytes, leydig cells of testes and in neurons in senile dementia.M/E coarse golden brown granular pigment, accumulates in central part of the cells around the nuclei.Brown atrophy of heart

Lipofuschin granules in cardiac myocytes ( H & E)

EXOGENOUS PIGMENTSIntroduced in the body byInhalationIngestionInoculation

Inhalation pigmentsPneumoconiosisOccupational lung diseases due to inhalation of carbon, silica, iron oxideAnthracosis- deposition of carbon particlesSilicosisAsbestosis

The condition is called pneumoconiosis or occupational hazards

Particles between 1-5 micrometer diameter are most dangerous

Pathogenicity depends upon size, solubility, cytotoxicity and the amount in the inhaled air

Phagocytosis of dust particles by alveolar macrophages provides protection

1- AnthracosisIt is deposition of carbon or coal dust in the lungs in horses and mules used in coal mines and dogs living in the smoky areas. Tattooing is a localized anthracosis

Carbon dust is mildly irritating and causes a slight fibrosis.

It is insoluble and persists in the tissues for life

2-SilicosisIt is perhaps most prevalent chronic occupational disease associated with silicon industries like glass etc

It is a slowly progressive, nodular, fibrosing pneumoconiosis

Silica is a powerful irritant and causes extreme fibrosis, predisposing to diseases like tuberculosis

3-AsbestosisThe condition is associated with asbestos industries and it is one of the most dangerous pneumoconiosesAsbestos particles cause severe irritation and fibrosisAsbestos is carcinogenic

4-PlumbismIt is pigmentation in the tissues resulting from the presence of lead and hydrogen sulphide.Lead poisoning may occur from licking of paints or from water in lead pipes.Microscopically lead is deposited in the tissues in combination with hydrogen sulphide as a black pigment.

Ingested pigmentsChronic ingestion of certain metals may produce pigmentation

ArgyriaChronic ingestion of silver compounds & results in brownish pigmentation in the skin, bowel and kidney.

Chronic lead poisoningBlue lines on teeth at the gumlines

Melanosis coli results from prolonged ingestion of certain cathartics.Carotenaemia yellowish red colouration of skin caused by excessive ingestion of carrots which contain carotene.

Injected pigments (tattooing)Pigments like india ink, cinnabar and carbon Prolonged use of ointments containing mercuryTattooing by pricking skin

SummaryEndogenousMelaninOchronosisHaemoprotein derived pigments- haemosiderin, haemozoin, bilirubi,porphyrins and lipofuschinExogenousInhalation InjectionIngestion

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