DISTURBANCES OF PIGMENT METABOLISM

Dr 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.Lipofuschin

EXOGENOUSInhaled pigmentsIngested pigmentsInjected pigments (tatooing)

Endogenous pigments Normal constituents of cells or accumulate under

special circumstancese.g MelaninOchronosisHaemoprotein derived pigmentsLipofuscin

Melanin Brown black, non haemoglobin derived

pigment Hair, skin, choroid of the eye, meninges

and adrenal medulla. Synthesis- in melanocytes and dendritic

cells

Stains for melanin Fontana silver method Dopa reaction Tyrosinase reaction Florescent microscopy

Disorders of pigmentation

HyperpigmentationGeneralisedFocal HypopigmentationGeneralisedFocal

Hyperpigmentation

GeneralisedAddison`s diseaseChloasmaChronic arsenical poisoning FocalCafeau lait spotsPeutz jegher`s syndromeMelanosis coliMelanotic tumorsLentigo

Hypopigmentation

Hypopigmentation 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

Ochronosis

Autosomal recessive disorder Deficiency of oxidase enzyme Homogentisic acid- deposited in

cartilage,joints, ligaments and tendons Alkaptonuria- black urine

Haemoprotein derived pigments

Haemosiderin Acid haematin (haemozoin) Bilirubin Porphyrins

Haemosiderin

Iron is stored in the tissues in 2 forms:FerritinHaemosiderin Prussian blue reaction Excessive 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 excess

Localised 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 haemozoin

Haemoprotein derived brown black pigment containing haeme iron in ferric form

Cannot be stained by prussian blue reaction Seen in chronic malaria, mismatch blood transfusion Formalin pigment

Bilirubin Normal non iron containing pigment present in bile Normal levels < 1mg/dl Excess bilirubin– jaundice Classification Prehepatic Hepatic Post hepaticExcess accumulation of bilirubin pigment—hepatocytes,

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.

Prehepatic Hepatic Post hepatic

Basic mechanism Hemolysis leading to increased production

Deficient uptake,c onjugation or excretion by hepatocytes

Deficient excretion due to obstruction

Type of bilirubin raised

Mainly unconjugated UC +C Both Mainly conjugated

Urine bilirubin absent present present

Urine urobilinogen Present Variable Decreased

Prototype Haemolytic anemia Viral hepatitis Common duct stone

PT Normal Abnormal not corrected with vit K

Abnormal corrected with vit K

Additional Features of hemolysis on blood smear

Marked rise of sr ALT & AST

Marked rise of sr ALP >3 times

Porphyrias

Porphyrins 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.

Lipofuschin Wear 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 PIGMENTS

Introduced in the body by Inhalation Ingestion Inoculation

Inhalation pigments

PneumoconiosisOccupational lung diseases due to inhalation of carbon,

silica, iron oxide Anthracosis- deposition of carbon particles Silicosis Asbestosis

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- Anthracosis It 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- Silicosis It 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-Asbestosis The condition is associated with asbestos industries and it is one

of the most dangerous pneumoconioses Asbestos particles cause severe irritation and fibrosis Asbestos is carcinogenic

4-Plumbism It 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 pigments

Chronic 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

Summary EndogenousMelaninOchronosisHaemoprotein derived pigments- haemosiderin,

haemozoin, bilirubi,porphyrins and lipofuschin ExogenousInhalation InjectionIngestion

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