This document summarizes different types of pigmentation disturbances. It describes endogenous pigments produced within the body like melanin, ochronosis, and hemoprotein derivatives. It also discusses exogenous pigments that enter the body through inhalation, injection, or ingestion. Examples are given like anthracosis from inhaled carbon particles, argyria from ingested silver, and tattoo pigments from injection. Disturbances can cause hyperpigmentation with excess pigment production or hypopigmentation with pigment loss. The document provides an overview of pigment metabolism and disorders of pigmentation.

1. DISTURBANCES OF PIGMENT
METABOLISM
Dr Neha Mahajan
MD Pathology

2. That impart color to tissues.
Abnormal pigmentation :
-excess normal
Decrease of normal
Normal pigment at abnormal site
Abnormal pigment
Pigments: heterogenous group
of substances

3.  Pigments are coloured substances present in
most living beings including humans.
 ENDOGENOUS
 EXOGENOUS

4. ENDOGENOUS
1.Melanin
2.Melanin like pigment
Alkaptonuria
Dubin johnson syndrome
3.Haemoprotein derived pigments
Haemosiderin
Acid haematin( haemozoin)
Bilirubin
Porphyrins
4.Lipofuschin
EXOGENOUS
Inhaled pigments
Ingested pigments
Injected pigments (tatooing)

5.  Endogenous pigments
Normal constituents of cells or accumulate under
special circumstances
e.g Melanin
Ochronosis
Haemoprotein derived pigments
Lipofuscin

6. Melanin
 Brown black, non haemoglobin derived
pigment
 Hair, skin, choroid of the eye, meninges
and adrenal medulla.
 Synthesis- in melanocytes and dendritic
cells

7. Stains for melanin
 Fontana silver method
 Dopa reaction
 Tyrosinase reaction
 Florescent microscopy

8. Disorders of pigmentation
 Hyperpigmentation
Generalised
Focal
 Hypopigmentation
Generalised
Focal

9. Hyperpigmentation
 Generalised
Addison`s disease
Chloasma
Chronic arsenical poisoning
 Focal
Cafeau lait spots
Peutz jegher`s syndrome
Melanosis coli
Melanotic tumors
Lentigo

10. 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.

11. Hypopigmentation
 Generalised hypopigmentation
Albinism
 Localised hyppopigmentation
Leucoderma
Vitiligo
Acquired focal hypopigmentation- leprosy,
healing of wounds, DLE,radiation dermatitis

12. Ochronosis
 Autosomal recessive disorder
 Deficiency of oxidase enzyme
 Homogentisic acid- deposited in
cartilage,joints, ligaments and tendons
 Alkaptonuria- black urine

13. Haemoprotein derived pigments
 Haemosiderin
 Acid haematin (haemozoin)
 Bilirubin
 Porphyrins

14. Haemosiderin
 Iron is stored in the tissues in 2 forms:
Ferritin
Haemosiderin
 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)

15. Effects of haemosiderin excess
 Localised haemosiderosis
 Generalised haemosiderosis

16. Localised haemosiderosis
Haemorrhage in tissue
Bruise or black eye
Brown induration of lung
Infarction

17. Generalised haemosiderosis( systemic or
diffuse)
Two types of patterns:
Parenchymatous depostion of haemosiderin- liver, pancreas,
kidney and heart.
Reticuloendothelial deposition- liver, spleen, bone marrow.

18. 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)
AD
Triad- liver cirrhosis, pancreatic damage & skin
pigmentation( bronze diabetes)
 Excessive intake of dietary iron
Bantu`s disease

19. Haemosiderin golden granules in liver H & E

20. Prussian blue stain

21. 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

22. Bilirubin
 Normal non iron containing pigment present in bile
 Normal levels < 1mg/dl
 Excess bilirubin– jaundice
 Classification Prehepatic
Hepatic
Post hepatic
Excess accumulation of bilirubin pigment—hepatocytes,
kupffer cells and bile sinusoids
Kernicterus

23. BILIRUBIN METABOLISM
Normal
Bilirubin
Metabolism

24. Jaundice
Hyperbilirubinemia:
Two forms:
Direct bilirubin:Conjugated with glucoronic acid
Indirect bilirubin: unconjugated, insoluble in
water.

26. 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

27. Porphyrias
 Porphyrins are tetrapyrroles which exists in 3 forms:
Haeme contains iron.
Chlorophyl contains magnesium
Cobalamin contains cobalt
Porphyria--- 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

28. 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

30. Porphyrias
 Erythropoeitic
Defective synthesis of haeme in RBC`s
Congenital: red urine due to presence of uroporphyrin I and
coproporphyrin I.
Skin highly photosensitive, red brown discolouration
Erythropoeitic: excess of protoporphyrin but no excess of
porphyrin in urine.
 Hepatic
Defective synthesis of haeme in liver.
Acute intermittent porphyria: acute episodes of 3 patterns:
abdominal, neurological and psychotic, no
photosensitivity
Excess delta aminolaevulinic acid and porphobilinogen in urine

31. Variegate porphyria
Photosensitivity.
Acute attacks of colicky abdominal pain & neurological
manifestations.
Hereditary porphyria
Porphyria cutanea tarda
Most common of all porphyrias.
Porhyrins collect in liver & small quantity excreted in urine.
Haemosiderosis----cirrhosis---- hepatocellular carcinoma.

32. 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

33. Lipofuschin granules in cardiac myocytes ( H & E)

34. EXOGENOUS PIGMENTS
Introduced in the body by
 Inhalation
 Ingestion
 Inoculation

35. Inhalation pigments
Pneumoconiosis
Occupational lung diseases due to inhalation of carbon,
silica, iron oxide
 Anthracosis- deposition of carbon particles
 Silicosis
 Asbestosis

36.  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

37. 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

38. 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

39. 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

40. 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.

41. Ingested pigments
 Chronic ingestion of certain metals may produce
pigmentation
Argyria
Chronic ingestion of silver compounds & results in brownish
pigmentation in the skin, bowel and kidney.
Chronic lead poisoning
Blue lines on teeth at the gumlines

42.  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 mercury
Tattooing by pricking skin

43. Summary
 Endogenous
Melanin
Ochronosis
Haemoprotein derived pigments- haemosiderin,
haemozoin, bilirubi,porphyrins and
lipofuschin
 Exogenous
Inhalation
Injection
Ingestion

44. Thank you