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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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